This research article summarizes a study encapsulating curcumin, a natural anti-cancer compound, in polymeric micelles for cancer therapy. The researchers synthesized a diblock copolymer micelle (PNPC) from methoxy polyethylene glycol and oleic acid to encapsulate curcumin. They showed that PNPC had high drug loading efficiency and stability. In vitro, PNPC significantly suppressed the proliferation of breast and liver cancer cell lines. In an animal model of breast cancer, PNPC treatment reduced tumor incidence and size compared to controls. PNPC also increased expression of pro-apoptotic genes and decreased expression of anti-apoptotic and proliferative genes in the tumors. The results suggest PNPC is a
This document summarizes a study that compared the cancer targeting abilities of doxorubicin-loaded multiwalled carbon nanotubes (MWCNTs) functionalized with either estrone or folic acid. Both in vitro and in vivo experiments using breast cancer cells found that the estrone-functionalized nanotubes showed preferential uptake and greater antitumor activity compared to other formulations, likely due to overexpression of estrogen receptors on the cancer cells. Pharmacokinetic studies also confirmed increased cancer targeting of the ligand-functionalized MWCNTs. The estrone formulation in particular significantly extended survival time in a mouse model compared to free doxorubicin and a control group.
This document summarizes an article that appeared in a journal published by Elsevier. The attached copy is provided to the author for non-commercial research and education purposes, including instruction and sharing with colleagues. Other uses such as reproduction, distribution, selling, licensing or posting to third party websites are prohibited. Authors are allowed to post their version of the article to their personal or institutional websites or repositories, with some restrictions. The document provides a link to Elsevier's policies on author rights.
Combined effects of PEGylation and particle size on uptake of PLGA particles ...Nanomedicine Journal (NMJ)
Abstract
Objective:
At the present study, relationship between phagocytosis of PLGA particles and combined effects of particle size and surface PEGylation was investigated.
Materials and Methods:
Microspheres and nanospheres (3500 nm and 700 nm) were prepared from three types of PLGA polymers (non-PEGylated and PEGylation percents of 9% and 15%). These particles were prepared by solvent evaporation method. All particles were labeled with FITC-Albumin. Interaction of particles with J744.A.1 mouse macrophage cells, was evaluated in the absence or presence of 7% of the serum by flowcytometry method.
Results:
The study revealed more phagocytosis of nanospheres. In the presence of the serum, PEGylated particles were phagocytosed less than non-PEGylated particles. For nanospheres, this difference was significant (P<0/05) and their uptake was affected by PEGylation degree. In the case of microsphere formulation, PEGylation did not affect the cell uptake. In the serum-free medium, the bigger particles had more cell uptake rate than smaller ones but the cell uptake rate was not influenced by PEGylation.
Conclusion:
The results indicated that in nanosized particles both size and PEgylation degree could affect the phagocytosis, but in micron sized particles just size, and not the PEGylation degree, could affect this.
The document describes research on developing doxorubicin-loaded, folic acid-conjugated multi-walled carbon nanotubes (DOX/FA-MWCNTs) for targeted cancer treatment. The nanotubes were engineered through purification, oxidation, and functionalization processes. Doxorubicin was loaded onto the nanotubes through pi-pi stacking interactions. In vitro studies found the DOX/FA-MWCNTs had high drug loading efficiency, controlled release, and preferential uptake by cancer cells. In vivo studies in tumor-bearing rats showed the DOX/FA-MWCNTs improved pharmacokinetics, biodistribution to tumors, and increased survival time compared to free doxorubicin
Russell and Burch first introduced the concept of the 3Rs (Replacement, Reduction, Refinement) in 1959 to promote more humane experimental techniques that replace animal use when possible, reduce the number of animals used, and refine experiments to minimize pain and distress. Some alternative methods discussed include in vitro tests using cell and tissue cultures, computer modeling, and reducing variables in study design. The global adoption of the 3Rs aims to establish non-animal approaches for toxicity testing and research.
This research article summarizes a study investigating potential artifacts in 1H NMR-based metabolomic studies on cell cultures due to contaminants from plastic cell culture dishes. The researchers found that brief rinsing or incubation of culture medium in plastic dishes eluted chemicals that could confound assays of certain metabolites. Extraction of "null samples" using perchloric acid, methanol-chloroform, or acetonitrile also produced artifacts from plastic dishes, though to a lesser extent with methanol and acetonitrile. The best practice is to run extraction of blank dishes with every batch of experiments to identify background contamination and provide a reference spectrum.
This document describes a study investigating the cancer targeting potential of docetaxel (DTX) loaded onto multi-walled carbon nanotubes (MWCNTs) conjugated with folic acid (FA) and poly(ethylene glycol) (PEG). DTX was loaded onto both FA-PEG-conjugated MWCNTs (DTX/FA-PEG-MWCNTs) and plain MWCNTs (DTX/MWCNTs). In vitro studies showed the DTX/FA-PEG-MWCNTs had higher cytotoxicity against MCF-7 breast cancer cells and arrested cells in the G2 phase more than DTX/MWCNTs or free drug. Pharmacokinetic studies in mice
The document discusses alternatives to animal toxicity testing for phototoxicity and carcinogenicity evaluation. It summarizes the 3T3 neutral red uptake photo toxicity test used to assess phototoxic potential in vitro. It also describes tests to detect genotoxic carcinogens like the Ames assay and mouse lymphoma assay, and non-genotoxic carcinogens using the Syrian hamster embryo cell transformation assay which can identify carcinogens through morphological transformation of cells.
This document summarizes a study that compared the cancer targeting abilities of doxorubicin-loaded multiwalled carbon nanotubes (MWCNTs) functionalized with either estrone or folic acid. Both in vitro and in vivo experiments using breast cancer cells found that the estrone-functionalized nanotubes showed preferential uptake and greater antitumor activity compared to other formulations, likely due to overexpression of estrogen receptors on the cancer cells. Pharmacokinetic studies also confirmed increased cancer targeting of the ligand-functionalized MWCNTs. The estrone formulation in particular significantly extended survival time in a mouse model compared to free doxorubicin and a control group.
This document summarizes an article that appeared in a journal published by Elsevier. The attached copy is provided to the author for non-commercial research and education purposes, including instruction and sharing with colleagues. Other uses such as reproduction, distribution, selling, licensing or posting to third party websites are prohibited. Authors are allowed to post their version of the article to their personal or institutional websites or repositories, with some restrictions. The document provides a link to Elsevier's policies on author rights.
Combined effects of PEGylation and particle size on uptake of PLGA particles ...Nanomedicine Journal (NMJ)
Abstract
Objective:
At the present study, relationship between phagocytosis of PLGA particles and combined effects of particle size and surface PEGylation was investigated.
Materials and Methods:
Microspheres and nanospheres (3500 nm and 700 nm) were prepared from three types of PLGA polymers (non-PEGylated and PEGylation percents of 9% and 15%). These particles were prepared by solvent evaporation method. All particles were labeled with FITC-Albumin. Interaction of particles with J744.A.1 mouse macrophage cells, was evaluated in the absence or presence of 7% of the serum by flowcytometry method.
Results:
The study revealed more phagocytosis of nanospheres. In the presence of the serum, PEGylated particles were phagocytosed less than non-PEGylated particles. For nanospheres, this difference was significant (P<0/05) and their uptake was affected by PEGylation degree. In the case of microsphere formulation, PEGylation did not affect the cell uptake. In the serum-free medium, the bigger particles had more cell uptake rate than smaller ones but the cell uptake rate was not influenced by PEGylation.
Conclusion:
The results indicated that in nanosized particles both size and PEgylation degree could affect the phagocytosis, but in micron sized particles just size, and not the PEGylation degree, could affect this.
The document describes research on developing doxorubicin-loaded, folic acid-conjugated multi-walled carbon nanotubes (DOX/FA-MWCNTs) for targeted cancer treatment. The nanotubes were engineered through purification, oxidation, and functionalization processes. Doxorubicin was loaded onto the nanotubes through pi-pi stacking interactions. In vitro studies found the DOX/FA-MWCNTs had high drug loading efficiency, controlled release, and preferential uptake by cancer cells. In vivo studies in tumor-bearing rats showed the DOX/FA-MWCNTs improved pharmacokinetics, biodistribution to tumors, and increased survival time compared to free doxorubicin
Russell and Burch first introduced the concept of the 3Rs (Replacement, Reduction, Refinement) in 1959 to promote more humane experimental techniques that replace animal use when possible, reduce the number of animals used, and refine experiments to minimize pain and distress. Some alternative methods discussed include in vitro tests using cell and tissue cultures, computer modeling, and reducing variables in study design. The global adoption of the 3Rs aims to establish non-animal approaches for toxicity testing and research.
This research article summarizes a study investigating potential artifacts in 1H NMR-based metabolomic studies on cell cultures due to contaminants from plastic cell culture dishes. The researchers found that brief rinsing or incubation of culture medium in plastic dishes eluted chemicals that could confound assays of certain metabolites. Extraction of "null samples" using perchloric acid, methanol-chloroform, or acetonitrile also produced artifacts from plastic dishes, though to a lesser extent with methanol and acetonitrile. The best practice is to run extraction of blank dishes with every batch of experiments to identify background contamination and provide a reference spectrum.
This document describes a study investigating the cancer targeting potential of docetaxel (DTX) loaded onto multi-walled carbon nanotubes (MWCNTs) conjugated with folic acid (FA) and poly(ethylene glycol) (PEG). DTX was loaded onto both FA-PEG-conjugated MWCNTs (DTX/FA-PEG-MWCNTs) and plain MWCNTs (DTX/MWCNTs). In vitro studies showed the DTX/FA-PEG-MWCNTs had higher cytotoxicity against MCF-7 breast cancer cells and arrested cells in the G2 phase more than DTX/MWCNTs or free drug. Pharmacokinetic studies in mice
The document discusses alternatives to animal toxicity testing for phototoxicity and carcinogenicity evaluation. It summarizes the 3T3 neutral red uptake photo toxicity test used to assess phototoxic potential in vitro. It also describes tests to detect genotoxic carcinogens like the Ames assay and mouse lymphoma assay, and non-genotoxic carcinogens using the Syrian hamster embryo cell transformation assay which can identify carcinogens through morphological transformation of cells.
This document discusses several in vitro methods for assessing the cytotoxicity of chemotherapeutic drugs, including assays using brine shrimp, MTT, sulforhodamine B, trypan blue dye, and acridine orange/ethidium bromide staining. It describes maintaining cell lines from cervical carcinoma and breast adenocarcinoma in culture, assessing cell viability, and preserving cells in liquid nitrogen. Specific methods are provided for assays including brine shrimp lethality, MTT, sulforhodamine B, trypan blue dye exclusion, acridine orange/ethidium bromide staining, and DNA fragmentation to evaluate the cytotoxic effects of test compounds on cultured malignant cell lines.
This document summarizes a study that investigated using a novel diblock copolymer called monomethoxy poly(ethylene glycol)-oleate (mPEG-OA) to deliver the anticancer drug curcumin to cancer cells. The researchers synthesized mPEG-OA and tested its ability to form micelles and polymersomes, encapsulate curcumin, and deliver the drug to cancer cells. They found that mPEG-OA had a low critical micelle concentration and could efficiently encapsulate curcumin. Curcumin-loaded mPEG-OA micelles and polymersomes showed improved cytotoxicity against cancer cells compared to free curcumin, indicating this copolymer is a promising nanocarrier for curc
This document provides an overview of 7 chapters focused on in situ and in vitro models for assessing drug absorption. The chapters cover models of the skin, small intestine, colon, buccal mucosa, nasal cavity, lung, and various epithelial and endothelial barriers. A variety of in situ and in vitro techniques are discussed, including perfused organ models, cell culture systems, and excised tissue preparations. The models vary in their complexity and ability to predict in vivo absorption, with in situ techniques generally providing a more physiologically relevant system compared to simpler in vitro methods.
CYP121 Drug Discovery (M. tuberculosis)Anthony Coyne
Fragment screening was used to target cytochrome P450 (CYP) enzymes from Mycobacterium tuberculosis. Thermal shift assays identified fragment hits against CYP121, which were validated by NMR. X-ray crystallography showed two binding modes. Fragment growing, merging, and linking yielded elaborated fragments with improved binding affinity down to 2 nM against CYP121, maintaining good ligand efficiency. Future work will further optimize compounds against CYP121 and screen other CYP enzymes to develop selective, potent inhibitors to treat tuberculosis.
The micronucleus assay is a test used to detect potential genotoxic compounds. It works by identifying micronuclei, which form during cell division from chromosome fragments or whole chromosomes damaged by genotoxins. The assay has regulatory approval and can be conducted in vitro using cell cultures or in vivo using rodents. Cells or animals are exposed to test compounds, cell division is blocked, and cells are analyzed microscopically for the presence of micronuclei to determine if the compound caused genetic damage. The micronucleus assay is a simple, reliable, and reproducible method for toxicological testing.
Validation Of Radiation Sterilization Dose For Proteases Immobilized On Aldeh...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
This study evaluated the in vitro skin phototoxicity of cosmetic formulations containing photounstable and photostable UV filters (octyl methoxycinnamate, benzophenone-3, avobenzone, octyl salicylate, 4-methylbenzilidene camphor) and vitamin A palmitate using two tests: the 3T3 Neutral Red Uptake Phototoxicity Test and the Human 3-D Skin Model In Vitro Phototoxicity Test. Avobenzone showed pronounced phototoxicity and vitamin A showed a tendency toward weak phototoxic potential. A synergistic effect of vitamin A palmitate on the phototoxicity of combinations containing avobenzone was observed
This document provides a list of 159 books related to drugs and the pharmaceutical sciences. The books cover a wide range of topics including pharmacokinetics, good manufacturing practices, drug delivery systems, clinical drug trials, pharmaceutical analysis, and regulation. The list indicates that expertise in the pharmaceutical field requires in-depth knowledge across many interrelated domains.
The document describes the development and validation of a UPLC-MS/MS method for quantifying terbinafine in human plasma. The method uses a simple liquid-liquid extraction technique, has a run time of less than 2 minutes, and a lower limit of quantification of 15 ng/mL. This high-throughput method requires a small plasma volume of 500 μL and was successfully applied to a bioequivalence study comparing two 250 mg terbinafine tablets in 44 healthy volunteers. The validated method was sensitive, selective, and accurate for quantifying terbinafine plasma concentrations up to 144 hours post-dose to determine pharmacokinetic parameters.
ABSTRACT- The anticancer drug arsenic trioxide is effective for acute promyelocytic leukemia. But the clinical trials are
restricted due to its potential side effects. Since the major part of arsenic metabolism and detoxification occurs in liver,
this organ faces the major threat. The hepatic side effects include fatty liver, fibrosis, and inflammation and hepatocyte
degeneration. Our study aimed to evaluate the protective potential of the fatty acid, docosahexaenoic acid, against adversities
of arsenic trioxide in an in vitro model, the Chang liver cells. Two preliminary dose standardization assays, cell
viability and lactate dehydrogenase release assays, were employed. The assays were performed as Pre-treatment,
Co-treatment and Post treatment experiments for a period of 24 hours. Arsenic trioxide at various doses (2.5, 5, 7.5, 10,
12.5 and 15 μM) showed a significant (p≤0.05) dose dependant reduction in cell viability along with a dose dependant
enhancement of lactate dehydrogenase release. However when the cells were treated with a combination of docosahexaenoic
acid at varying concentrations (50, 75, 100, 125 and 150 μM), the above mentioned conditions were found to be
reversed in Pre-treatment and Co-treatment experiments, but not in Post treatment. The most effective combination was
found to be 10 μM arsenic trioxide with 100 μM of docosahexaenoic acid in both Pre-treatment and Co- treatment studies.
Thus the preliminary assays of our study showed that docosahexaenoic acid administration as Pre-treatment or
Co-treatment can aid in reducing arsenic trioxide induced hepatotoxicity. Further studies are required to elucidate the mechanisms
behind the protective effects.
Key Words– Arsenic trioxide, hepatotoxicity, docosahexaenoic acid, cell damage
This document outlines the syllabus for the subject Biopharmaceutics and Pharmacokinetics at Dr. Babasaheb Ambedkar Marathwada University. The syllabus covers 14 sections that include topics such as absorption, distribution, metabolism, elimination of drugs, pharmacokinetic models, bioavailability and bioequivalence. Some key areas covered are factors affecting drug absorption, distribution and elimination processes in the body, pharmacokinetic parameters and concepts such as volume of distribution, clearance and half-life. Mathematical treatments of compartment models and methods to determine pharmacokinetic parameters are also included.
Piroxicam Nanostructured Lipid Carrier Drug Delivery SystemYogeshIJTSRD
This document describes a study that developed and evaluated a piroxicam (PXM) nanostructured lipid carrier (NLC) gel for topical delivery. PXM-loaded NLCs were prepared using the high-pressure homogenization method and characterized for particle size, drug entrapment efficiency, and in vitro drug release. The optimized NLC formulation was incorporated into a gel and evaluated for properties such as viscosity, drug content, and in vitro diffusion. Ex vivo skin irritation studies showed the gel caused no irritation. In vivo tests in rats demonstrated the NLC gel effectively reduced carrageenan-induced paw edema, indicating anti-inflammatory effects. Overall, the NLC gel was found to be a promising delivery
Nanoparticle based oral delivery of vaccinesAshok Patidar
Nanoparticle based oral delivery of vaccines presents an attractive alternative to other delivery routes. Nanoparticles can protect vaccine antigens from gastrointestinal fluids and transport them across the intestinal barrier for uptake by immune cells. Various nanoparticle formulations are being explored as oral vaccine carriers due to their ability to co-deliver antigens and adjuvants. However, challenges remain in ensuring sufficient antigen integrity and transportation. Further development is needed to design robust and scalable nanoparticle vaccine formulations.
Review on Phytoconstituents and Pharmacological Activities of Leaves of Ormoc...Premier Publishers
Several plants possess a variety of biologically active compounds. Among them Ormocarpum cochinchinense, belonging to the family Fabaceae is an important traditional plant, which potentially shows good effect in bone fracture healing. The objectives of this paper are categorized in 3 groups. First, reviewing the available literature on the potential health effects of Ormocarpum cochinchinense, second, providing an insight to the potential implications of the studies reviewed in the context of possible compounds and therapeutic applications in health management, and third, identifying the fields of interests for future researches.
This document describes the development and validation of a rapid turbidimetric assay to quantify the potency of tigecycline in lyophilized powder samples. The assay uses Staphylococcus aureus and measures absorbance to determine antibiotic concentration over time. The method was validated and shown to have good linearity from 3 to 4.32 μg/mL, selectivity, precision, robustness, and 99.74% accuracy. The validated turbidimetric assay provides a simple, sensitive, and reliable alternative for routine quality control of tigecycline formulations.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
A nanocarrier is nano material being used as a transport module for another substance, such as a drug. Commonly used nanocarriers include micelles, polymers, carbon-based materials, liposomes and other substances.Nanocarriers are currently used in drug delivery and their unique characteristics demonstrate potential use in chemotherapy. Nanocarriers include polymer conjugates, polymeric nanoparticles, lipid-based carriers, dendrimers, carbon nanotubes, and gold Nanoparticles.Lipid-based carriers include both liposomes and micelles.
Examples of gold nanoparticles are gold nanoshells and nanocages.Different types of nonmaterial being used in nano carriers allows for hydrophobic and hydrophilic drugs to be delivered throughout the body.
potential problem with nanocarriers is unwanted toxicity from the type of nonmaterial being used. Inorganic nonmaterial can also be toxic to the human body if it accumulates in certain cell organelles new research is being conducted to invent more effective, safer nanocarriers.
Nano pharmaceuticals offer the ability to detect diseases at much earlier stages and the diagnostic applications could build upon conventional procedures using nano particles.
Nano pharmaceuticals represent an emerging field where the sizes of the drug particle or a therapeutic delivery system work at the nanoscale.
Nano pharmaceuticals have enormous potential in addressing this failure of traditional therapeutics which offers site-specific targeting of active agents.
Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms.
Gold nanoparticles tagged with short segments of DNA can be used for detection of genetic sequence in a sample.
Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots into polymeric microbeads.
Nan pore technology for analysis of nucleic acids converts strings of nucleotides directly into electronic signatures.C-dots (Cornell dots) are the smallest silica-based nanoparticles with the size <10 nm.
There are three main reasons for the popularity of herbal medicine
1. There is a growing concern over the reliance and safety of drugs.
2. Modern medicine is failing to effectively treat many of the most common health condition.
3. Many natural measures are being shown to produce better results than drugs or surgery without the side effects
Knowledge-based chemical fragment analysis in protein binding sitesCresset
This document discusses an approach to selecting likely binding molecules for a protein target based on analyzing known protein-ligand interactions from the Protein Data Bank (PDB). It describes extracting "fragments" from ligands that form hydrogen bonds to common amino acids like Aspartic acid, Glutamic acid, Arginine, and Histidine. These fragments are analyzed to determine common structural motifs that preferentially interact with certain amino acid side chains. This knowledge could help medicinal chemists design new compounds likely to bind a given protein binding site.
The document summarizes a presentation on nanoparticles. It begins with an introduction defining nanoparticles as particulate dispersions between 10-1000nm in size. It then discusses the ideal properties of nanoparticles for drug delivery including stability and non-toxicity. Some advantages are increased therapeutic efficacy and targeted drug delivery. Potential disadvantages include limited targeting abilities and toxicity. Different types of nanoparticles are described such as nanocapsules, nanospheres, solid lipid nanoparticles and polymeric nanoparticles. Methods of preparation include polymerization, ionic gelation and use of preformed polymers. Evaluation methods are also summarized such as assessing particle size, drug content and in vitro drug release.
Identification of Bioactive Compounds in the acetone extract of Daedalea eleg...AI Publications
Daedalea elegans is a Nigerian wild (non-edible) higher fungus with great potentials in the pharmaceutical, textile, cosmetics and food industry. This current study investigates the bioactive compounds that can be found in the acetone extract of D. elegans using Gas Chromatography-Mass Spectrometry (GC-MS). There were twenty-eight compounds identified to be present in the acetone extract of the fungi under study and these are Benzoic acid (0.40%), Nonanoic acid (0.14%), Oxetane, 2,2,4-trimethyl- (0.28%), n-Decanoic acid (0.09%), Phthalimide (0.44%) Dodecanoic acid (0.24%), E-2-Hexenyl benzoate (0.21%), 2,4-Difluorobenzene, 1-benzyloxy- (0.16%), Tetratetracontane (0.55%), Isopropylphosphonic acid, fluoroanhydryde (0.28%), Benzene, (1-methylundecyl)- (0.21%), Tetradecanoic acid (0.76%), Cyclohexanepropanol, .alpha.,2,2,6-tetrame (0.56%), Pentadecanoic acid (0.71%), E-2-Hexenyl benzoate (0.32%), Pentadecanoic acid (0.97%), 1-Decanol, 2-hexyl- (0.46%), 9-Tetradecenal, (Z) (1.67), n-Hexadecanoic acid (23.59%) is the second most abundant, Phthalic acid, butyl undecyl ester (1.08%), Eicosanoic acid (0.79%), 9,12-Octadecadienoic acid (Z,Z)- (44.64%) was the highest in quantity, Octadecanoic acid (6.98%), Bis(2-ethylhexyl) phthalate (2.64%), 2,2,4-Trimethyl-3-(3,8,12,16-tetramethyl-heptadeca-3,7,11,15-tetraenyl)-cyclohexanol (1.95%), 9(11)-Dehydroergosteryl benzoate (8.37%), 9(11)-Dehydroergosteroltosylate (1.28%), 4,6-Decadienal, 8-ethyl-10-[4-hydroxy-8-(2-hydroxypropyl)-3,9 (0.22%). These compounds possess activities which includes but not limited to cancer chemotherapy, antifeedant against pine weevil, antifungi agent in topical therapeutic preparation, anti-inflammatory, immunomodulatory, anti-convulsant, antioxidants, hypocholesterolemic, anti-androgenic, nematicide, analgesic, intermediate for food-grade additives, lubricants, greases, rubber, dyes and plastic, antineoplastic agent, biosynthesis of prostaglandins and cell membrane to mention a few. This study has been able to show that D. elegans is a good source of bioactive compounds with great potentials that can be harnessed in various industries.
This document provides details on the equipment required for manufacturing different pharmaceutical dosage forms according to Schedule M regulations. It discusses equipment for external preparations like ointments and creams, oral liquids, tablets, powders, capsules, ophthalmic preparations, and parenteral preparations. For each dosage form, it lists specific mixing, blending, filling and packaging equipment. It also provides recommended minimum area requirements. The goal is to ensure manufacturing takes place in properly equipped and controlled areas to maintain quality and prevent cross-contamination.
The document discusses liposomes, including their principle, definition, discovery, composition, mechanisms of formation, classification, preparation methods, drug encapsulation, characterization, stability, uses, and commercial products. Liposomes are spherical vesicles composed of phospholipid bilayers that can encapsulate drugs for targeted delivery. They were discovered in 1965 and offer advantages like biocompatibility and protection of drugs, though production costs are high and leakage can occur.
This document discusses several in vitro methods for assessing the cytotoxicity of chemotherapeutic drugs, including assays using brine shrimp, MTT, sulforhodamine B, trypan blue dye, and acridine orange/ethidium bromide staining. It describes maintaining cell lines from cervical carcinoma and breast adenocarcinoma in culture, assessing cell viability, and preserving cells in liquid nitrogen. Specific methods are provided for assays including brine shrimp lethality, MTT, sulforhodamine B, trypan blue dye exclusion, acridine orange/ethidium bromide staining, and DNA fragmentation to evaluate the cytotoxic effects of test compounds on cultured malignant cell lines.
This document summarizes a study that investigated using a novel diblock copolymer called monomethoxy poly(ethylene glycol)-oleate (mPEG-OA) to deliver the anticancer drug curcumin to cancer cells. The researchers synthesized mPEG-OA and tested its ability to form micelles and polymersomes, encapsulate curcumin, and deliver the drug to cancer cells. They found that mPEG-OA had a low critical micelle concentration and could efficiently encapsulate curcumin. Curcumin-loaded mPEG-OA micelles and polymersomes showed improved cytotoxicity against cancer cells compared to free curcumin, indicating this copolymer is a promising nanocarrier for curc
This document provides an overview of 7 chapters focused on in situ and in vitro models for assessing drug absorption. The chapters cover models of the skin, small intestine, colon, buccal mucosa, nasal cavity, lung, and various epithelial and endothelial barriers. A variety of in situ and in vitro techniques are discussed, including perfused organ models, cell culture systems, and excised tissue preparations. The models vary in their complexity and ability to predict in vivo absorption, with in situ techniques generally providing a more physiologically relevant system compared to simpler in vitro methods.
CYP121 Drug Discovery (M. tuberculosis)Anthony Coyne
Fragment screening was used to target cytochrome P450 (CYP) enzymes from Mycobacterium tuberculosis. Thermal shift assays identified fragment hits against CYP121, which were validated by NMR. X-ray crystallography showed two binding modes. Fragment growing, merging, and linking yielded elaborated fragments with improved binding affinity down to 2 nM against CYP121, maintaining good ligand efficiency. Future work will further optimize compounds against CYP121 and screen other CYP enzymes to develop selective, potent inhibitors to treat tuberculosis.
The micronucleus assay is a test used to detect potential genotoxic compounds. It works by identifying micronuclei, which form during cell division from chromosome fragments or whole chromosomes damaged by genotoxins. The assay has regulatory approval and can be conducted in vitro using cell cultures or in vivo using rodents. Cells or animals are exposed to test compounds, cell division is blocked, and cells are analyzed microscopically for the presence of micronuclei to determine if the compound caused genetic damage. The micronucleus assay is a simple, reliable, and reproducible method for toxicological testing.
Validation Of Radiation Sterilization Dose For Proteases Immobilized On Aldeh...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
This study evaluated the in vitro skin phototoxicity of cosmetic formulations containing photounstable and photostable UV filters (octyl methoxycinnamate, benzophenone-3, avobenzone, octyl salicylate, 4-methylbenzilidene camphor) and vitamin A palmitate using two tests: the 3T3 Neutral Red Uptake Phototoxicity Test and the Human 3-D Skin Model In Vitro Phototoxicity Test. Avobenzone showed pronounced phototoxicity and vitamin A showed a tendency toward weak phototoxic potential. A synergistic effect of vitamin A palmitate on the phototoxicity of combinations containing avobenzone was observed
This document provides a list of 159 books related to drugs and the pharmaceutical sciences. The books cover a wide range of topics including pharmacokinetics, good manufacturing practices, drug delivery systems, clinical drug trials, pharmaceutical analysis, and regulation. The list indicates that expertise in the pharmaceutical field requires in-depth knowledge across many interrelated domains.
The document describes the development and validation of a UPLC-MS/MS method for quantifying terbinafine in human plasma. The method uses a simple liquid-liquid extraction technique, has a run time of less than 2 minutes, and a lower limit of quantification of 15 ng/mL. This high-throughput method requires a small plasma volume of 500 μL and was successfully applied to a bioequivalence study comparing two 250 mg terbinafine tablets in 44 healthy volunteers. The validated method was sensitive, selective, and accurate for quantifying terbinafine plasma concentrations up to 144 hours post-dose to determine pharmacokinetic parameters.
ABSTRACT- The anticancer drug arsenic trioxide is effective for acute promyelocytic leukemia. But the clinical trials are
restricted due to its potential side effects. Since the major part of arsenic metabolism and detoxification occurs in liver,
this organ faces the major threat. The hepatic side effects include fatty liver, fibrosis, and inflammation and hepatocyte
degeneration. Our study aimed to evaluate the protective potential of the fatty acid, docosahexaenoic acid, against adversities
of arsenic trioxide in an in vitro model, the Chang liver cells. Two preliminary dose standardization assays, cell
viability and lactate dehydrogenase release assays, were employed. The assays were performed as Pre-treatment,
Co-treatment and Post treatment experiments for a period of 24 hours. Arsenic trioxide at various doses (2.5, 5, 7.5, 10,
12.5 and 15 μM) showed a significant (p≤0.05) dose dependant reduction in cell viability along with a dose dependant
enhancement of lactate dehydrogenase release. However when the cells were treated with a combination of docosahexaenoic
acid at varying concentrations (50, 75, 100, 125 and 150 μM), the above mentioned conditions were found to be
reversed in Pre-treatment and Co-treatment experiments, but not in Post treatment. The most effective combination was
found to be 10 μM arsenic trioxide with 100 μM of docosahexaenoic acid in both Pre-treatment and Co- treatment studies.
Thus the preliminary assays of our study showed that docosahexaenoic acid administration as Pre-treatment or
Co-treatment can aid in reducing arsenic trioxide induced hepatotoxicity. Further studies are required to elucidate the mechanisms
behind the protective effects.
Key Words– Arsenic trioxide, hepatotoxicity, docosahexaenoic acid, cell damage
This document outlines the syllabus for the subject Biopharmaceutics and Pharmacokinetics at Dr. Babasaheb Ambedkar Marathwada University. The syllabus covers 14 sections that include topics such as absorption, distribution, metabolism, elimination of drugs, pharmacokinetic models, bioavailability and bioequivalence. Some key areas covered are factors affecting drug absorption, distribution and elimination processes in the body, pharmacokinetic parameters and concepts such as volume of distribution, clearance and half-life. Mathematical treatments of compartment models and methods to determine pharmacokinetic parameters are also included.
Piroxicam Nanostructured Lipid Carrier Drug Delivery SystemYogeshIJTSRD
This document describes a study that developed and evaluated a piroxicam (PXM) nanostructured lipid carrier (NLC) gel for topical delivery. PXM-loaded NLCs were prepared using the high-pressure homogenization method and characterized for particle size, drug entrapment efficiency, and in vitro drug release. The optimized NLC formulation was incorporated into a gel and evaluated for properties such as viscosity, drug content, and in vitro diffusion. Ex vivo skin irritation studies showed the gel caused no irritation. In vivo tests in rats demonstrated the NLC gel effectively reduced carrageenan-induced paw edema, indicating anti-inflammatory effects. Overall, the NLC gel was found to be a promising delivery
Nanoparticle based oral delivery of vaccinesAshok Patidar
Nanoparticle based oral delivery of vaccines presents an attractive alternative to other delivery routes. Nanoparticles can protect vaccine antigens from gastrointestinal fluids and transport them across the intestinal barrier for uptake by immune cells. Various nanoparticle formulations are being explored as oral vaccine carriers due to their ability to co-deliver antigens and adjuvants. However, challenges remain in ensuring sufficient antigen integrity and transportation. Further development is needed to design robust and scalable nanoparticle vaccine formulations.
Review on Phytoconstituents and Pharmacological Activities of Leaves of Ormoc...Premier Publishers
Several plants possess a variety of biologically active compounds. Among them Ormocarpum cochinchinense, belonging to the family Fabaceae is an important traditional plant, which potentially shows good effect in bone fracture healing. The objectives of this paper are categorized in 3 groups. First, reviewing the available literature on the potential health effects of Ormocarpum cochinchinense, second, providing an insight to the potential implications of the studies reviewed in the context of possible compounds and therapeutic applications in health management, and third, identifying the fields of interests for future researches.
This document describes the development and validation of a rapid turbidimetric assay to quantify the potency of tigecycline in lyophilized powder samples. The assay uses Staphylococcus aureus and measures absorbance to determine antibiotic concentration over time. The method was validated and shown to have good linearity from 3 to 4.32 μg/mL, selectivity, precision, robustness, and 99.74% accuracy. The validated turbidimetric assay provides a simple, sensitive, and reliable alternative for routine quality control of tigecycline formulations.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
A nanocarrier is nano material being used as a transport module for another substance, such as a drug. Commonly used nanocarriers include micelles, polymers, carbon-based materials, liposomes and other substances.Nanocarriers are currently used in drug delivery and their unique characteristics demonstrate potential use in chemotherapy. Nanocarriers include polymer conjugates, polymeric nanoparticles, lipid-based carriers, dendrimers, carbon nanotubes, and gold Nanoparticles.Lipid-based carriers include both liposomes and micelles.
Examples of gold nanoparticles are gold nanoshells and nanocages.Different types of nonmaterial being used in nano carriers allows for hydrophobic and hydrophilic drugs to be delivered throughout the body.
potential problem with nanocarriers is unwanted toxicity from the type of nonmaterial being used. Inorganic nonmaterial can also be toxic to the human body if it accumulates in certain cell organelles new research is being conducted to invent more effective, safer nanocarriers.
Nano pharmaceuticals offer the ability to detect diseases at much earlier stages and the diagnostic applications could build upon conventional procedures using nano particles.
Nano pharmaceuticals represent an emerging field where the sizes of the drug particle or a therapeutic delivery system work at the nanoscale.
Nano pharmaceuticals have enormous potential in addressing this failure of traditional therapeutics which offers site-specific targeting of active agents.
Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms.
Gold nanoparticles tagged with short segments of DNA can be used for detection of genetic sequence in a sample.
Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots into polymeric microbeads.
Nan pore technology for analysis of nucleic acids converts strings of nucleotides directly into electronic signatures.C-dots (Cornell dots) are the smallest silica-based nanoparticles with the size <10 nm.
There are three main reasons for the popularity of herbal medicine
1. There is a growing concern over the reliance and safety of drugs.
2. Modern medicine is failing to effectively treat many of the most common health condition.
3. Many natural measures are being shown to produce better results than drugs or surgery without the side effects
Knowledge-based chemical fragment analysis in protein binding sitesCresset
This document discusses an approach to selecting likely binding molecules for a protein target based on analyzing known protein-ligand interactions from the Protein Data Bank (PDB). It describes extracting "fragments" from ligands that form hydrogen bonds to common amino acids like Aspartic acid, Glutamic acid, Arginine, and Histidine. These fragments are analyzed to determine common structural motifs that preferentially interact with certain amino acid side chains. This knowledge could help medicinal chemists design new compounds likely to bind a given protein binding site.
The document summarizes a presentation on nanoparticles. It begins with an introduction defining nanoparticles as particulate dispersions between 10-1000nm in size. It then discusses the ideal properties of nanoparticles for drug delivery including stability and non-toxicity. Some advantages are increased therapeutic efficacy and targeted drug delivery. Potential disadvantages include limited targeting abilities and toxicity. Different types of nanoparticles are described such as nanocapsules, nanospheres, solid lipid nanoparticles and polymeric nanoparticles. Methods of preparation include polymerization, ionic gelation and use of preformed polymers. Evaluation methods are also summarized such as assessing particle size, drug content and in vitro drug release.
Identification of Bioactive Compounds in the acetone extract of Daedalea eleg...AI Publications
Daedalea elegans is a Nigerian wild (non-edible) higher fungus with great potentials in the pharmaceutical, textile, cosmetics and food industry. This current study investigates the bioactive compounds that can be found in the acetone extract of D. elegans using Gas Chromatography-Mass Spectrometry (GC-MS). There were twenty-eight compounds identified to be present in the acetone extract of the fungi under study and these are Benzoic acid (0.40%), Nonanoic acid (0.14%), Oxetane, 2,2,4-trimethyl- (0.28%), n-Decanoic acid (0.09%), Phthalimide (0.44%) Dodecanoic acid (0.24%), E-2-Hexenyl benzoate (0.21%), 2,4-Difluorobenzene, 1-benzyloxy- (0.16%), Tetratetracontane (0.55%), Isopropylphosphonic acid, fluoroanhydryde (0.28%), Benzene, (1-methylundecyl)- (0.21%), Tetradecanoic acid (0.76%), Cyclohexanepropanol, .alpha.,2,2,6-tetrame (0.56%), Pentadecanoic acid (0.71%), E-2-Hexenyl benzoate (0.32%), Pentadecanoic acid (0.97%), 1-Decanol, 2-hexyl- (0.46%), 9-Tetradecenal, (Z) (1.67), n-Hexadecanoic acid (23.59%) is the second most abundant, Phthalic acid, butyl undecyl ester (1.08%), Eicosanoic acid (0.79%), 9,12-Octadecadienoic acid (Z,Z)- (44.64%) was the highest in quantity, Octadecanoic acid (6.98%), Bis(2-ethylhexyl) phthalate (2.64%), 2,2,4-Trimethyl-3-(3,8,12,16-tetramethyl-heptadeca-3,7,11,15-tetraenyl)-cyclohexanol (1.95%), 9(11)-Dehydroergosteryl benzoate (8.37%), 9(11)-Dehydroergosteroltosylate (1.28%), 4,6-Decadienal, 8-ethyl-10-[4-hydroxy-8-(2-hydroxypropyl)-3,9 (0.22%). These compounds possess activities which includes but not limited to cancer chemotherapy, antifeedant against pine weevil, antifungi agent in topical therapeutic preparation, anti-inflammatory, immunomodulatory, anti-convulsant, antioxidants, hypocholesterolemic, anti-androgenic, nematicide, analgesic, intermediate for food-grade additives, lubricants, greases, rubber, dyes and plastic, antineoplastic agent, biosynthesis of prostaglandins and cell membrane to mention a few. This study has been able to show that D. elegans is a good source of bioactive compounds with great potentials that can be harnessed in various industries.
This document provides details on the equipment required for manufacturing different pharmaceutical dosage forms according to Schedule M regulations. It discusses equipment for external preparations like ointments and creams, oral liquids, tablets, powders, capsules, ophthalmic preparations, and parenteral preparations. For each dosage form, it lists specific mixing, blending, filling and packaging equipment. It also provides recommended minimum area requirements. The goal is to ensure manufacturing takes place in properly equipped and controlled areas to maintain quality and prevent cross-contamination.
The document discusses liposomes, including their principle, definition, discovery, composition, mechanisms of formation, classification, preparation methods, drug encapsulation, characterization, stability, uses, and commercial products. Liposomes are spherical vesicles composed of phospholipid bilayers that can encapsulate drugs for targeted delivery. They were discovered in 1965 and offer advantages like biocompatibility and protection of drugs, though production costs are high and leakage can occur.
Niosomes are non-ionic surfactant based vesicles that can be used for drug delivery. They have several advantages including increased drug stability, biocompatibility and ability to target delivery. Niosomes are prepared using non-ionic surfactants which form bilayer vesicles encapsulating the drug. Preparation methods include thin film hydration, sonication, microfluidization. Niosomes can be characterized for size, entrapment efficiency and release kinetics. They have applications in delivery of anti-cancer drugs, peptides, vaccines and transdermal delivery due to their ability to enhance skin permeation.
Niosomes are novel drug delivery systems composed of non-ionic surfactants and cholesterol. They can encapsulate both hydrophilic and lipophilic drugs. Niosomes are prepared using methods like ether injection, film hydration, sonication, and microfluidization. Key factors that affect niosome formation include the surfactant used, addition of cholesterol, and hydration temperature. Niosomes offer advantages over liposomes like improved stability and the ability to entrap both hydrophilic and hydrophobic drugs. Niosomes find applications in targeted drug delivery through routes like transdermal, parenteral, oral and for ophthalmic and radiopharmaceutical uses.
Niosomes are non-ionic surfactant-based vesicles that can be used for drug delivery. They are similar in structure to liposomes but offer advantages over liposomes such as greater stability. Niosomes are typically composed of cholesterol and non-ionic surfactants like spans or tweens. They can be prepared using methods such as ether injection, film hydration, sonication, or microfluidization. Niosomes can encapsulate both hydrophilic and hydrophobic drugs and are being researched for applications like cancer treatment, transdermal drug delivery, and as carriers for peptide drugs. Advantages of niosomes include biocompatibility, ability to modify drug release properties, and no special storage conditions required
This document summarizes research on gastroretentive drug delivery systems (GRDDS). GRDDS are designed to retain drugs in the stomach for extended periods of time to allow sustained release of drugs. The document discusses various approaches to GRDDS including floating systems, mucoadhesive systems, high density systems, and swollen or expanded systems. It also summarizes several research publications on recent advances in GRDDS technology including development of bioadhesive microspheres and floating microspheres for oral drug delivery.
The document discusses cosmetics and their uses for different areas of the body. It notes that developing expertise in cosmetics requires knowledge in dermatology, biochemistry, cosmetic chemistry, and research and can take over 30 years of training. It then lists different body areas and examples of common cosmetic preparations used for each area. Finally, it discusses considerations for developing cosmetics including anatomy, physiology, skin care needs, hygiene needs, and common dermatological diseases.
This document provides an overview of osmotic drug delivery systems. It discusses the basic components and principles of osmosis that osmotic drug delivery systems utilize. The key components discussed include the drug, osmogen, semipermeable membrane, and factors that affect drug release such as solubility, osmotic pressure, delivery orifice size, and membrane type. A variety of osmotic pump designs are also briefly mentioned.
The document discusses niosomes, a novel drug delivery system. Niosomes are non-ionic surfactant vesicles similar in structure to liposomes but with advantages like being more stable and requiring no special storage conditions. The document outlines factors that affect niosome preparation such as the surfactant type and ratio, drug properties, and addition of cholesterol. Several methods for preparing niosomes are also described, including film hydration, ether injection, sonication, and microfluidization. Niosomes can encapsulate both hydrophilic and hydrophobic drugs and offer benefits like controlled release, increased drug stability and bioavailability, and targeted drug delivery.
Niosomes are a novel drug delivery system, in which the medication is encapsulated in a vesicle. The vesicle is composed of a bilayer of non-ionic surface active agents and hence the name niosomes.
The document discusses niosomes, which are vesicles composed of nonionic surfactants and cholesterol. Niosomes can encapsulate drugs and deliver them to target sites in the body, providing advantages over other drug delivery systems. The document outlines the general characteristics, advantages, disadvantages, structure, preparation methods, and applications of niosomes. It also compares niosomes to liposomes and discusses factors that affect the physicochemical properties of niosomes.
Liposomes are spherical vesicles made of concentric phospholipid bilayers. They were first produced in 1961 and can range in size from 20 nm to several micrometers. Liposomes provide advantages like selective targeting to tumors, increased drug efficacy, and reduced toxicity, but also have disadvantages such as high production costs and drug leakage. Common methods for preparing liposomes include film hydration, ethanol injection, and detergent removal.
This document discusses cosmetic chemistry concepts including atoms, molecules, elements, compounds, mixtures, pH, acidity, alkalinity, and the acid mantle. It then covers how cosmetics can be classified based on their physical and chemical properties, including powders, suspensions, ointments, solutions, emulsions, and soaps. Specific examples are provided for each classification. Makeup products like face powder and foundation are also briefly discussed.
Liposomes are spherical vesicles made of phospholipid bilayers that can encapsulate hydrophilic or hydrophobic drugs. They range in size from 25nm to 5000nm. This document discusses the structure of liposomes and their components, including phospholipids and cholesterol. Various preparation methods are described, such as lipid film hydration, ethanol injection, and detergent removal. Liposomes offer advantages for drug delivery, such as the ability to encapsulate different drug types and provide controlled release. They can be classified based on structure, method of preparation, composition, and specialty type.
This document provides an overview of liposomes. It begins with an introduction describing liposomes as concentric bilayer vesicles composed mainly of phospholipids and cholesterol. It then covers the mechanism of liposome formation, classifications, biological fate, preparation methods, characterization techniques, advantages and disadvantages, and applications. Preparation methods discussed include physical dispersion, solvent dispersion, detergent solubilization, and various size reduction/increase techniques. Characterization includes assessing size, shape, lamellarity, surface charge, drug release, and encapsulation efficiency using tools like microscopy, NMR, and chromatography.
Effective in vitro gene delivery to murine cancerous brain cells using carbon...Nanomedicine Journal (NMJ)
Abstract
Objective(s):
Carbon nanotube (CNT) has been widely applied at molecular and cellular levels due to its exceptional properties. Studies based on conjugation of CNTs with biological molecules indicated that biological activity is preserved. Polyethylenimine (PEI) is explored in designing novel gene delivery vectors due to its ability to condense plasmid DNA through electrostatic attraction. In this study functionalization and grafting polyethylenimine onto the surface of carbon nanotube was used to improve the solubility and biocompatibility.
Materials and Methods:
The effect of molecular weight of polymer on final efficacy of vectors has been investigated using three different molecular weights of polymer. In this study no linker was used and both segments (PEI and CNT) were directly attached resulted in the synthesis of three different vectors. Synthesized vectors were tested for their ability to condense plasmid DNA and cellular toxicity using ethidium bromide and MTT assays. Size and Zeta potential of nanoparticles was determined using Malvern zeta sizer. Evaluation of transfection efficiency of vectors was carried out on N2A cell line by different methods including qualitative fluorescence imaging, flow cytometry and luciferase assay.
Results:
All three synthesized vectors bear positive surface charges with sizes in the range of 85-190 nm. More than 80 percent of treated cells were viable and in the case of V25 significant improvement in reducing cytotoxicity compared to unmodified polymer was observed. Obtained results indicated that vector containing PEI 1.8 kDa has the greatest improvement in terms of its transfection efficiency compared to unmodified polymer.
Conclusion:
Conjugation of PEI with carbon nanotube les to new vectors with lowered cytotoxicity and higher transfection efficiency. The highest transfection efficiency was obtained with the lowest molecular weight PEI.
Experimental and theoretical solubility advantage screening of bi-component s...Maciej Przybyłek
This document describes an experimental and theoretical study to screen potential solubilizers for curcumin. In the experimental phase, the solubility of curcumin was measured in binary mixtures with 24 excipients. The highest solubility enhancement was found with pyrogallol, caffeine, theophylline, and nicotinamide. A theoretical QSPR model was then developed using molecular descriptors to predict solubility. This model was applied to screen over 230,000 compounds and predict solubility for curcumin analogs and naturally occurring turmerones to identify new excipients.
This study evaluated the cytotoxicity of pegylated nanoliposomal cisplatin on ovarian cancer cells. Methoxypolyethylene glycol propionaldehyde was synthesized and characterized. Nanoliposomes encapsulating cisplatin were prepared using the reverse phase evaporation method and characterized. The nanoliposomes had a mean diameter of 125 nm and negative zeta potential. Cytotoxicity tests on ovarian cancer cells showed the IC50 of nanoliposomal cisplatin was lower than free cisplatin, indicating the nanoliposomal formulation was more cytotoxic. This study demonstrates pegylated nanoliposomal cisplatin has potential as a more effective cisplatin delivery system for ovarian cancer treatment.
Abstract
Abstract
Among synthetic carriers, dendrimers with the more flexible structure have attracted a great deal of researchers’ attention in the field of gene delivery. Followed by the promising results upon hydrophobic modification on polymeric structures in our laboratory, alkylcarboxylated poly (propylenimine)-based carriers were synthesized by nucleophilic substitution of amines with alkyl moieties and were further characterized for their physicochemical and biological characteristics for plasmid DNA delivery. Although not noticeably effective gene transfer activity for hexanoate- and hexadecanoate-modified series was observed, but alkylation by decanoic acid significantly improved the transfection efficiency of the final constructs up to 60 fold in comparison with unmodified poly(propylenimine) (PPI). PPI modified by 10-bromodecanoic acid at 50% grafting, showed significantly higher gene expression at c/p ratio of 2 compared to Superfect as positive control.
Overall, modification of PPI with 50% primary amines grafting with 10-bromodecanoic acid could increase the transfection efficiency which is occurred at lower c/p ratio when compared to Superfect, i.e. less amount of modified vector is required to exhibit the same efficiency as Superfect. Therefore, the obtained constructs seem to be safer carriers for long-term gene therapy applications.
Formulation and in vitro evaluation of quercetin loaded carbon nanotubes for ...IRJET Journal
This document presents a study that formulated and evaluated quercetin-loaded carbon nanotubes for cancer targeting. Specifically, it:
1) Developed a quercetin-loaded drug delivery system using functionalized single-walled carbon nanotubes conjugated with chitosan.
2) Found that the highest drug loading efficiency of 38% was achieved at 4°C and with an equal initial weight ratio of drug to carrier.
3) Demonstrated that the drug delivery system was stable under neutral pH but effectively released quercetin under acidic pH similar to the tumor environment.
4) Showed that the quercetin-conjugated carrier had significantly higher cytotoxicity against HeLa
This document describes research into the microbial synthesis of platinum nanoparticles using Saccharomyces boulardii and evaluation of the anticancer activity of the synthesized platinum nanoparticles. Key findings include:
1) Platinum nanoparticles were successfully synthesized using the cell free extract of S. boulardii when reacted with chloroplatinic acid.
2) Various parameters like metal salt concentration, temperature, cellmass concentration, pH, and reaction time were optimized to control the yield and properties of the synthesized nanoparticles.
3) The synthesized platinum nanoparticles showed anticancer activity against A431 and MCF-7 cell lines with IC50 values between 57-100 μg/ml, indicating potential for use as an antic
ST8 micellar/niosomal vesicular nanoformulation for delivery of naproxen in c...Vahid Erfani-Moghadam
This document describes a study that developed a micellar/niosomal vesicular nanoformulation using squalene and Tween 80 (ST8MNV) to deliver the drug naproxen (NPX) for potential anti-inflammatory and anticancer applications. The ST8MNV exhibited high encapsulation efficiency of 99.5% for NPX. In vitro tests showed the ST8MNV nanoformulation significantly reduced the half maximal inhibitory concentration of NPX in four cancer cell lines, suggesting it is a promising drug delivery system to improve the cytotoxic effects of NPX for future studies.
Evaluation of the Impact of Biofield Treatment on Physical and Thermal Proper...wilhelm mendel
In the present study, the influence of biofield treatment on physical and thermal properties of Casein Enzyme Hydrolysate (CEH) and Casein Yeast Peptone (CYP) were investigated. The control and treated samples were characterized by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), Thermo Gravimetric Analysis (TGA), particle size and surface area analysis. The FTIR results revealed that biofield treatment has caused reduction of amide group (amide-I and amide-II) stretching vibration peak that is associated with strong intermolecular hydrogen bonding in treated CEH as compared to control. However, no significant changes were observed in FTIR spectrum of treated CYP. The TGA analysis of treated CEH showed a substantial improvement in thermal stability which was confirmed by increase in maximum thermal decomposition temperature (217°C) as compared to control (209°C). Similarly, the treated CYP also showed enhanced thermal stability as compared to control. DSC showed increase in melting temperature of treated CYP as compared to control. However the melting peak was absent in DSC of treated CEH which was probably due to rigid chain of the protein. The surface area of treated CEH was increased by 83% as compared to control. However, a decrease (7.3%) in surface area was observed in treated CYP. The particle size analysis of treated CEH showed a significant increase in average particle size (d50) and d99 value (maximum particle size below which 99% of particles are present) as compared to control sample. Similarly, the treated CYP also showed a substantial increase in d50 and d99 values which was probably due to the agglomeration of the particles which led to formation of bigger microparticles. The result showed that the biofield treated CEH and CYP could be used as a matrix for pharmaceutical applications.
Evaluation of the Impact of Biofield Treatment on Physical and Thermal Proper...rachelsalk
In the present study, the influence of biofield treatment on physical and thermal properties of Casein Enzyme Hydrolysate (CEH) and Casein Yeast Peptone (CYP) were investigated. The control and treated samples were characterized by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), Thermo Gravimetric Analysis (TGA), particle size and surface area analysis. The FTIR results revealed that biofield treatment has caused reduction of amide group (amide-I and amide-II) stretching vibration peak that is associated with strong intermolecular hydrogen bonding in treated CEH as compared to control. However, no significant changes were observed in FTIR spectrum of treated CYP. The TGA analysis of treated CEH showed a substantial improvement in thermal stability which was confirmed by increase in maximum thermal decomposition temperature (217°C) as compared to control (209°C). Similarly, the treated CYP also showed enhanced thermal stability as compared to control. DSC showed increase in melting temperature of treated CYP as compared to control. However the melting peak was absent in DSC of treated CEH which was probably due to rigid chain of the protein. The surface area of treated CEH was increased by 83% as compared to control. However, a decrease (7.3%) in surface area was observed in treated CYP. The particle size analysis of treated CEH showed a significant increase in average particle size (d50) and d99 value (maximum particle size below which 99% of particles are present) as compared to control sample. Similarly, the treated CYP also showed a substantial increase in d50 and d99 values which was probably due to the agglomeration of the particles which led to formation of bigger microparticles. The result showed that the biofield treated CEH and CYP could be used as a matrix for pharmaceutical applications.
Formulation and Evaluation of Moxifloxacin Loaded Alginate Chitosan Nanoparti...pharmaindexing
This document describes the formulation and evaluation of moxifloxacin-loaded alginate-chitosan nanoparticles for treating tuberculosis. Moxifloxacin nanoparticles were prepared using an ionic gelation method with varying polymer ratios and drug concentrations. Formulation MF3, with a drug concentration of 50 mg, exhibited the highest encapsulation efficiency, drug loading, and rate of recovery. In vitro drug release from MF3 was sustained over 96 hours with no significant changes observed after 3 months of stability testing. Scanning electron microscopy confirmed the nanoparticles had a discrete spherical structure without aggregation.
Centchroman loaded PLGA nanoparticles were developed using emulsification-solvent evaporation and nano-precipitation methods. The nanoparticles were characterized for particle size, polydispersity index, zeta potential, drug entrapment efficiency and in-vitro drug release. Particle size was analyzed using dynamic light scattering and found to be in the range of 100-200 nm. Drug entrapment efficiency was determined using centrifugation-based direct and indirect methods. In-vitro dissolution studies showed sustained release of centchroman from nanoparticles over 8 hours compared to plain drug.
Moringa Oleifera aqueous leaf extract inhibits the growth of pancreatic cancer cell lines by down-regulating the NF-κB signaling pathway and increasing the cytotoxic effect of chemotherapy. The extract reduced the viability of three pancreatic cancer cell lines in a dose-dependent manner. It induced cell cycle arrest and apoptosis in Panc-1 cells by reducing levels of proteins involved in the NF-κB pathway. When combined with cisplatin chemotherapy, the extract synergistically enhanced the cytotoxic effect on Panc-1 cells. The study demonstrates that Moringa Oleifera extract can potentiate the efficacy of chemotherapy in pancreatic cancer by inhibiting the NF-κB pathway that contributes to chemoresistance.
CYP2A6_HPLC_PK_2015 New Simple Method for Coumarin in Liver Cytochrome of RatsWael Ebied
This document describes the development and validation of a new liquid chromatography method for determining coumarin and its 7-hydroxy metabolite as a marker of cytochrome P450 2A6 activity in rats. The method uses a C18 column and isocratic mobile phase to separate coumarin, 7-hydroxycoumarin, and an internal standard. The method was validated and showed good linearity, precision, and accuracy. This validated method was then applied to study the effect of resveratrol, sulforaphane, and thymoquinone on hepatic CYP2A6 activity in spontaneously hypertensive rats.
This document provides a synopsis for a Master's thesis project titled "Formulation and Evaluation of Fast Dissolving Films of Lisinopril". The project aims to develop fast dissolving films of the hypertension drug Lisinopril to improve patient compliance. Literature on fast dissolving drug delivery systems and films has been reviewed. The planned work involves preparing Lisinopril films using natural and synthetic polymers through various techniques and evaluating the films for properties like drug content, dissolution, and pharmacodynamics. If successful, the fast dissolving Lisinopril films could provide quick action and ease of administration benefits for hypertension patients.
ISSN 2347-2251
It appears that you're describing the scope of a scientific journal. This journal covers a wide range of topics related to both Pharmaceutical Sciences and Biological Sciences of the journalism journals.
The Indo-American Journal of Pharma and Bio Sciences is an online international journal that publishes articles quarterly.It's important to note that the specific policies, guidelines, and the editorial board of IAJPB may change over time, so it's advisable to visit the journal's official website or contact the journal of the research on journaling.
This document describes a study that evaluated the pharmacokinetic/pharmacodynamic (PK/PD) relationships of a novel biotin carboxylase inhibitor called PD-0162819 against Haemophilus influenzae 3113 using in vitro infection models. Static concentration time-kill and one-compartment chemostat experiments were conducted. AUC/MIC ratio best explained efficacy compared to Cmax/MIC and T>MIC. Static effects and 99.9% killing were achieved at AUC/MIC values of 500 and 600, respectively. A semi-mechanistic PK/PD model was developed to describe bacterial growth and drug effects over time.
Formulation and evaluation of gelatin microspheres loaded with fenofibrateVimal Patel
The document summarizes a study that formulated and evaluated gelatin microspheres loaded with the drug fenofibrate using a coacervation and phase separation method. Two microsphere formulations were developed with different drug to polymer ratios and evaluated for properties such as particle size, encapsulation efficiency, in vitro drug release, and stability. The results showed the microspheres had particle sizes between 5-10μm and encapsulation efficiencies between 70-97%. In vitro drug release studies found one formulation released the drug over 12 hours in a sustained manner. The study concluded this formulation was suitable for oral sustained release of fenofibrate.
2. 2 BioMed Research International
nanoparticles has promising results for the poor water solu-
ble hydrophobic agents like curcumin. Feasible preparation
and use, size fitness, environmental sustainability, and shell
viability are all important factors for a suitable carrier [8].
According to some studies, encapsulated form of curcumin
improves its medical properties and solubility [9]. Previous
studies showed that dendrosome, a diblock nanostructure
made by oleic acid (OA) and polyethylene glycol (PEG, 400
Dalton) with anticancer and proapoptosis effects, is a suitable
option for curcumin encapsulation [10–12]. In the present
research, we used modified 2000 Dalton molecular weight
monomethoxy-PEG (mPEG) for curcumin encapsulation.
Recently our research group evaluated morphology and
physical behavior of mPEG2000-OA [13]. Based on CMC
measurement, this novel nanocarrier can be considered as an
appropriate drug delivery system for curcumin delivery in
cancer cells. A unique feature of mPEG2000-OA is the ease
with which the structure of their monomers can be varied
in order to provide suitable, inert drug porters for target
cells. In this study, we exploited mPEG2000-OA for curcumin
encapsulation as polymeric nanoparticle curcumin (PNPC)
and investigated its efficiency, drug loading, and stability with
more focus on clinical observations, hematological/blood
chemistry tests, and histological examinations. In addition,
PNPC’s protective and therapeutic effects were also assessed
in an animal model of breast cancer. Our results shed new
light on PNPC potential biocompatibility in in vitro and in
vivo biological systems.
2. Materials and Methods
2.1. Materials. Curcumin (>99%), doxorubicin hydrochlo-
ride, cyclophosphamide, ketamine, and xylazine were pur-
chased from Sigma Aldrich Co. (St. Louis, MO, USA). Mate-
rials for the polymeric nanocarrier (OM2000) preparation
including oleoyl chloride and methoxy polyethylene glycol
2000 (mPEG 2000) were got from Sigma-Aldrich Co. (St.
Louis, MO, USA). Chloroform and triethyl amine were
also purchased from Merck-Serono Company (Germany).
The human hepatocellular (HuH-7), mouse mammary (4T1)
carcinoma cell lines, and normal human fibroblast cells were
procured from Pasteur Institute of Iran (Pasteur Institute,
Tehran, Iran). Polyclonal mouse anti-rat/rabbit Bax, Bcl-2,
and CD31 antibodies (DAKO Corporation, USA) and rabbit
monoclonal antibody against Ki-67 (Thermo Fisher Scientific
Inc., San Jose, CA) were purchased.
2.2. The Study Design. Studies were conducted in five series
of experiments including (i) PNPC synthesis, (ii) PNPC
stability and drug loading, (iii) PNPC effects on cell viability
of mammary and hepatocellular carcinoma cells, (iv) PNPC
acute and chronic toxicity, and (v) PNPC protective and
therapeutic effects on animal model of breast cancer.
2.3. Animals. All animal studies have been conducted
according to relevant national and international guidelines of
the Weatherall report and Institutional Animal Care and Use
Committee (IACUC) of Tehran University of Medical Sci-
ences. Inbred female BALB/c mice (6–8 weeks old, purchased
from Iran Pasteur Institute) were maintained under 12-hour
dark and light cycle, with free access to food and water.
2.4. Polymeric Nanocarrier Synthesis. Polymeric nanoparticle
(PNP, OM2000) was synthesized by esterification of oleoyl
chloride (3.01 g, 0.01 mol) and methoxy polyethylene glycol
2000 (20 g, 0.01 mol) in the presence of triethyl amine (1.2 g,
0.012 mol) and chloroform as solvent at 25∘
C for 2 h (see
Supplemental Figure 1 in Supplementary Materials avail-
able online at http://dx.doi.org/10.1155/2015/824746). Triethyl
amine hydrochloride was filtered from organic phase. Chlo-
roform was then evaporated and OM2000 dried in a 40∘
C
vacuum oven for 4 h with 96% purity. Fourier transform
infrared (FT-IR) spectroscopic measurements in the potas-
sium bromide (KBr) pellets were done using a Perkin-Elmer
spectrometer. The 1
H NMR spectrums were carried out using
Bruker 400 MHZ in DMSO-d5.
2.5. Critical Micelle Concentration Determination. Critical
micelle concentration (CMC) of PNP was determined by
detecting shifts in the pyrene fluorescence absorbance spectra
[14]. In this regard, 3 mL of pyrene solution (6 × 10−6
M)
in acetone was added to a glass test tube and evaporated to
remove the solvent. Then, 5 mL of PNP (0.005 to 1 mg/mL)
was conjugated with phosphate-buffered saline (PBS; 0.01 M,
pH 7.4) added to the glass test tubes to reach to 6 × 10−7
M
pyrene final concentration. The solutions were vortexed and
conditioned at 37∘
C overnight. Fluorescence excitation spec-
tra of pyrene (300–350 nm) were measured at an emission
wavelength of 390 nm with slit widths of 2.5 and 5.0 nm
(Perkin-Elmer Fluorimeter, USA) for excitation and emis-
sion, respectively. The fluorescence excitation shifts from 334
to 339 nm were used to determine CMC of the polymeric
nanocarrier.
2.6. PNPC Physical Properties. Dynamic light scattering
(DLS) and atomic force microscopy (AFM) were carried
out to evaluate alterations in the zeta-potential, particle size,
particle size distribution, shape, and polydispersity index
(PdI) of the polymeric nanoparticle [14–16]. Nanoparticle
zeta-potential and size distribution of PNPC (0.01 M PBS,
pH 7.4) were analyzed by DLS (Zetasizer NanoZS, Malvern
Instruments, UK) using an argon laser beam at 633 nm and
90∘
scattering angle. To determine PNPC shape, a drop of
PNPC solution (0.05 mg/mL) was placed on freshly cleaved
mica and was allowed to dry at room temperature. The
sample was then mounted on a microscope scanner and
imaged in semicontact mode with AFM (JPK Instruments
Co., Germany).
2.7. PNPC Encapsulation Efficiency and Drug Loading. In
this section, measurements were performed in triplicate.
Different concentrations of curcumin (2 to 25 mg) in acetone
solution were mixed with 100 mg nanocarrier in 3 mL of water
and rotated with rotary evaporator till acetone evaporation.
PNPC was filtered using 0.22 𝜇m syringe filter to remove
3. BioMed Research International 3
nonencapsulated curcumin and then lyophilized. To disrupt
micellar or vesicle structures, 10 mg lyophilized PNPC was
dissolved in 1 mL methanol and vortexed with ultrasonic
waves for 10 min to ensure encapsulated curcumin release.
Curcumin concentration was then determined with spec-
trophotometer at 425 nm in comparison with methanol cali-
bration curve for curcumin. Drug loading (DL) and encapsu-
lation efficiency (EE) of curcumin/nanocarrier micelles were
finally quantified utilizing the following equation [15, 16]:
Drug loading content (%)
=
weight of curcumin in micelles
weight of micelles
× 100,
Encapsulation efficiency (%)
=
weight of micelled curcumin
weight of feeding curcumin
× 100.
(1)
2.8. PNPC Preparation. Curcumin (6 mg) was dissolved in
acetone and added into nanocarrier solution (100 mg/3 mL
water) and then mixed and rotated with rotary evaporator
for acetone evaporation. PNPC was filtered using 0.22 𝜇m
syringe filter to remove nonencapsulated curcumin. The
complex was then lyophilized and used for next experiments
[13].
2.9. Stability Assays. PNPC aqueous solution was kept at
4∘
C for 24 h and ten months at dark room temperature.
Precipitation indicates PNPC instability, while clear solution
confirms its stability [17]. Dissolved lyophilized samples in
water were made by manual shaking without additional
heating or sonication. PNPC size and distribution were
compared with freshly prepared PNPC by DLS [18]. At the
end of the first week, curcumin loaded content and size
distribution of PNPC were compared with freshly prepared
PNPC by spectroscopy and DLS, respectively.
2.10. MTT Assay. HuH-7, 4T1, and normal fibroblast cell
lines were grown in Dulbecco’s modified Eagle’s medium
(DMEM; GIBCO, USA) containing 10% fetal bovine serum
(FBS; GIBCO, USA) at 37∘
C in humid atmosphere. Cell
viability measured by MTT (3-[4,5-dimethylthiazol-2-yl] 2,
5-diphenyltetrazolium bromide) assay [19]. Curcumin stock
solution (100 𝜇M) in DMEM was prepared from 10 mM
curcumin in methanol. Methanol percentage in the final
solution was lower than 0.4% v/v. Identical cell numbers (1 ×
106
cells) in 200 𝜇L DMEM containing 10% FBS were seeded
in triplicate on 96-well plates and incubated overnight. Cells
were subsequently treated with various concentrations (0,
10, 20, 30, and 40 𝜇M) of PNPC, PNP alone, curcumin,
and doxorubicin (as positive control) for 24 h and 48 h.
Afterwards, 20 𝜇L of MTT (5 mg/mL) was added to each well
and incubated for an additional 4 h followed by adding 200 𝜇L
of dimethyl sulfoxide. Relative cell viability was then deter-
mined using a 96-well plate reader (TECAN, Switzerland) at
540 nm.
2.11. Dosing Procedure. One hundred sixteen BALB/c mice
were used to study the acute and chronic toxicity of PNPC
[20]. In acute toxicity protocol, 2000 mg/kg of PNPC was
given as starting dose. Then, doses of 2000, 1000, 500, 250,
125, 62.5, 31.25, and 15.63 mg/kg body weight of PNPC and
PNP were intraperitoneally injected. Animals were eutha-
nized after 24 h. In case of studying 24 h adverse reactions,
the dose was adjusted based on the average toxicity and the
last tolerated dose for the new group of mice. Organ damage,
histopathological findings, abnormal hematological/blood
chemical indices, reduced organ weight ratio, and body
weight changes were amongst the toxicity signs.
Based on the acute toxicity results, chronic toxicity was
carried out using doses of 125, 62.5, 31.25, and 15.63 mg/kg
of PNPC and PNP for 7 consecutive days. The dose with no
adverse reactions during 24 h was assigned as the survival
dose. Survived animals were weighed on a daily basis and
euthanized one week later. Hematology, blood chemistry,
and histopathological tests were carried out. Vital organs
including heart, liver, spleen, lung, brain, and kidney were
excised and weighed.
2.12. Hematology, Blood Chemistry, and Histopathological
Tests. Animals were decapitated under general anesthesia to
evaluate hematology, clinical chemistry, and histopathology
parameters. Blood samples were taken for clinical chemistry
tests. Total leukocyte count (WBC), erythrocyte count (RBC),
platelets (Plt), hemoglobin (Hgb), hematocrit (Hct), mean
cell volume (MCV), mean corpuscular hemoglobin (MCH)
and mean corpuscular hemoglobin concentration (MCHC),
neutrophils, lymphocytes, eosinophils, and monocytes were
measured using an animal blood counter (Celltac; Nihon
Kohden, Tokyo, Japan). Plasma urea nitrogen (BUN), creati-
nine (Cr), sodium (Na), potassium (K), chloride (Cl), bicar-
bonate (HCO3−
), calcium (Ca), magnesium (Mg), lactate
(Lac), osmolarity (Osm), and glucose (Glu) were determined
using CCX System (CCX WB; Nova Biomedical, USA).
Plasma alkaline phosphatase (ALP), albumin (ALB), total
bilirubin (T.Bil), direct bilirubin (D.Bil), gamma-glutamyl
transpeptidase (GGT), alanine transaminase (ALT), and
aspartate transaminase (AST) were also measured (Autoanal-
yser Model Biotecnica, BT 3500, Rome, Italy). In addition,
liver, kidney, brain, lung, spleen, and heart tissue samples
were fixed and preserved in 4% buffered formaldehyde for
at least 24 h. Tissue blocks were prepared and evaluated for
histopathological changes.
2.13. Tumor Transplantation. Spontaneous mouse mammary
tumor (SMMT) was aseptically separated from the breast-
cancer-bearing BALB/c mice, cut into pieces of less than
0.3 cm3
, and subcutaneously transplanted into the animals’
left flank under ketamine and xylazine (10 mg/kg, i.p.) anes-
thesia [21].
2.14. PNPC Protective Effects on an Animal Model of Breast
Cancer. Sixteen mice were divided into two equal groups
of nontreated (control) and treated for the study of PNPC
protective effects on a typical animal model of breast cancer.
4. 4 BioMed Research International
PNPC was given for 24 days, from 3 days before to 21 days
after tumor transplantation. Animal survival rate and tumor
take rate were measured at the end of the study.
2.15. PNPC Therapeutic Effects on an Animal Model of Breast
Cancer. Twenty-four mice were equally divided into neg-
ative control, positive control, and PNPC groups to study
nanocurcumin therapeutic effects on mice breast cancer.
PNPC was given for 24 days after tumor transplantation
from day 14 up to day 38. In the positive control group,
doxorubicin (5 mg/kg) and cyclophosphamide (2 mg/mouse)
were intraperitoneally coadministered in three separate doses
for three consecutive weeks. Normal saline was also given
in the negative control group. Tumor volume was measured
weekly by a digital vernier caliper (Mitutoyo, Japan) and
reported according to the following formula [21]:
𝑉 =
1
6 (𝜋𝐿𝑊𝐷)
, (2)
where 𝐿 = length, 𝑊 = width, and 𝐷 = depth.
2.16. Histopathological Assay. The breast tumoral and adja-
cent nontumoral mucosal tissues were fixed in 10% formalde-
hyde, passaged, and embedded in paraffin. Paraffin blocks
were then sectioned by 3–5 𝜇m thickness for hematoxylin
and eosin (H&E) staining [22]. Slides were studied using
OLYMPUS-BX51 microscope. Digital photos were taken with
OLYMPUS-DP12 camera and graded by the Scarff-Bloom-
Richardson Scale [23].
2.17. Immunohistochemistry Examinations. Immunohisto-
chemistry was carried out on 3–5 𝜇m tissue sections taken
from the formalin-fixed paraffin blocks using avidin-biotin
immunoperoxidase method [24]. For tumor cells’ apoptotic
and angiogenic studies, sections were stained with polyclonal
mouse anti-rat/rabbit Bax, Bcl-2, and CD31 antibodies
(DAKO Corporation, USA) according to the manufacturer’s
instructions. Briefly, the paraffin sections were deparaffinized
with xylene and rehydrated through a series of descending
graded ethanol solutions. Slides kept into TBS-EDTA
buffer and put into a microwave oven for 15 min at 90∘
C.
Endogenous peroxidase activity was blocked by 0.3% H2O2
buffer incubation for 15 min. Biotinylated secondary antibody
and avidin-biotin complex with horseradish peroxidase were
applied followed by chromogen 3,3
-diaminobenzidine
addition (Sigma Chemical).
To study tumor cell proliferative activity, sections were
treated with 3% (v/v) H2O2 at room temperature, blocked
with 10% (v/v) goat serum or rabbit serum (Nichirei, Tokyo,
Japan), and incubated with a rabbit monoclonal antibody
against Ki-67 (Thermo Fisher Scientific Inc., San Jose,
CA). Sections were then incubated with biotinylated goat
anti-rabbit IgG (Nichirei) and a solution of streptavidin-
conjugated horseradish peroxidase (Nichirei) according to
the manufacturer’s recommendations.
Criteria used to evaluate Bax, Bcl-2, CD31, and Ki67
markers were based on the estimated proportion of positive
cells and estimated average staining intensity of positive cells
in cytoplasm (for Bax), membrane (for CD31), nucleus (for
Ki67), and membrane, cytoplasm or nucleus (for Bcl-2).
Semiquantitative score was adopted as follows [22, 24]:
no staining: 0;
faint/barely staining up to 1/3 of cells: 1,
moderate staining in 1/3 to 1/2 of cells: 2,
strong staining in more than 1/2 of cells: 3.
2.18. Statistical Analysis. Analysis of variance (ANOVA) and
Tukey’s post hoc tests were used for comparison between
groups. Two-tailed Student’s 𝑡-tests were used when compar-
ing two groups. Differences in tumor incidence (percentage
of animals with breast cancer) were analyzed by Fisher’s exact
probability test. Values were represented as mean ± SEM. 𝑃 <
0.05 was considered to be statistically significant. Statistical
analysis was done using SPSS statistical software version 14.0.
3. Results
3.1. The FT-IR Spectrum of the Polymeric Carrier. The FT-IR
spectrum of the polymeric carrier showed stretching band of
C–H aliphatic at 2889, 2947, and 2960 cm−1
. C=O stretching
vibration of ester bands could be seen at 1736 cm−1
. C–
H bending vibration of CH2 and C–H bending vibration
of CH3 can be seen in 1467 and 1343 cm−1
, respectively.
C–O stretching vibration was at 1112 cm−1
as broad band
(Supplemental Figure 2).
3.2. The 1
H NMR Spectrum of the Polymeric Carrier. Supple-
mental Figure 3 shows 1
H NMR spectrum of the polymeric
carrier from 0 to 6.5 ppm in DMSO-d5. Saturated protons in
fatty ester were at 0.8, 1.2, 1.5, 2, and 2.3 ppm. CH2 protons
between unsaturated bonds in linoleate and linolenate were at
2.6 ppm. Residual DMSO-d5
1
H NMR signal was at 2.5 ppm
(Supplemental Figure 3(a)). DMSO-d5 water was in 3.3 ppm
as broad band. CH3 protons of mPEG were in 3.2 ppm. CH2
protons of mPEG ethylene oxide units were multipeaks in
3.5 ppm (Supplemental Figure 3(b)). CH2 protons of mPEG
ethylene oxide connected to fatty acid chloride were at 4.1 and
4.2 ppm. C–H oleate, linoleate, and linolenate were in 5.3, 6.2,
and 6.4 ppm, respectively (Supplemental Figure 3(c)).
3.3. Critical Micelle Concentration of Polymeric Nanocarrier.
Concentration at crossover point in Figure 1 shows CMC
of nanocarrier at 339/334 nm intensity ratio and nanocarrier
concentration logarithm. As noted, CMC value is very low
near 0.03 g/L. With increasing nanocarrier concentration,
florescence intensity has significantly risen (Figure 1).
3.4. PNPC Physical Properties. The size, morphology, and
polydispersity of the nanoparticles were evaluated using
dynamic light-scattering technique (DLS) and AFM methods
(Figure 2). The results show that two forms of particles
were produced in the process of synthesis, micelles and
polymersomes with the average size of 18.33 ± 5.32 nm and
99.44 ± 65 nm, respectively. The freshly prepared PNP with
5. BioMed Research International 5
mPEG-OA
mPEG (control)
2.5
2.0
1.5
1.0
0.5
0.0
0.00
−0.25
−0.50
−0.75
−1.50
−1.75
−2.00
−2.25
−1.00
−2.50
−1.25
−2.75
−3.00
CMC
logC (concentration (g/L))
I(339/334)
I
(a)
0
200
400
600
320 330 340 350
Excitation wavelength (nm)
mPEG-control
0.005
0.125
0.5
1
Florescenceintensity(a.u.)
(b)
Figure 1: Determination of CMC of (a) pyrene excitation spectra shift and (b) four datasets from ten are displayed to simply show the below
and above CMC concentration when micelles developed. C: the concentration of polymeric nanoparticle (PNP).
0
5
10
15
20
0.1 1 10 100 1000 10000
freshly prepared
after one week
average result of all samples
Volume(%)
Record 108: mPEG-OA nanoparticles,
Record 109: mPEG-OA nanoparticles,
Record 111: mPEG-OA nanoparticles,
Size distribution by volume
Size (d·nm)
(a)
0.10.0 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
142nm
35nm
(𝜇m)
(b)
Figure 2: Morphology and particle size distribution of PNPC. (a) Red line shows average results of freshly prepared PNPC samples (0–25%
curcumin encapsulation in PNP). It shows three particle sizes, 18.3 ± 5.3, 65.5 ± 30, and 283 ± 112 nm. Green line shows average results of
PNPC samples after one week at 25∘
C (0–25% curcumin encapsulation in PNP). It shows one particle size of 99.4 ± 42.6 nm. Blue line shows
average result of all samples with two sizes, 18.3 ± 5.3 (they seem to be micelles) and 99.4 ± 65 nm (they seem to be polymersomes). (b) Atomic
force microscopy (AFM) results. AFM image of redissolved PNPC after freeze-drying (0.05 mg/mL) also showed two particle forms and sizes.
Smaller particles (<40 nm) seem to be micelles and larger particles (>40 nm) seem to be polymersomes.
different curcumin content (0–25%) were monodisperse (PdI
= 0.332 ± 0.13), with three particle forms 53.5% micelles
(18.33 ± 5.3 nm), 38.8% polymersomes (65.5 ± 30 nm), and
7.5% polymersomes (283.6 ± 112 nm). However, after one
week of incubation at 25∘
C, the particle forms changed to
be more monodisperse (PdI = 0.182 ± 0.072) with 100%
polymersomes (99.44 ± 42.56 nm). The results of AFM
analysis show that the shape of PNPC was in accordance
with DLS analysis (Figure 2(b)). However, compared to DLS
analysis, the AFM results show the larger size of PNPC
which can be attributed to the expansion of spherical micelles
or vesicles (polymersomes) in mica surface after drying its
solution. Moreover, the AFM results show that in PNPC
graph the z-dimensional (height) bar is smaller than X- and
Y-dimensional bars which support this claim (Supplemental
Figure 4). The PNPC is indeed stable in the presence of oleate
in this nanoformulation. The negative zeta-potential was
found to be −29.3 ± 5.2 mV at concentration of 0.05 mg/mL
6. 6 BioMed Research International
Curcumin loading10
10 12 14 16 18 20 22 24 26
9
8
8
7
6
6
5
4
4
3
2
2
1
0
0
Drugloading(%)
Curcumin (mg/100 mg nanocarrier)
(a)
Encapsulation efficiency120
100
80
60
40
20
40
0
8 12 16 20 24
Encapsulationefficiency(%)
Curcumin (mg/100 mg nanocarrier)
(b)
Figure 3: Encapsulation efficiency and drug loading of curcumin in PNPC. (a) Encapsulation efficiency (EE) and (b) drug loading (DL) of
curcumin.
0
5
10
15
20
25
0.1 1 10 100 1000 10000
Size distribution by volume
Record 125: nanocurcumin fresh
Record 126: nanocurcumin after one week
Volume(%)
Size (d·nm)
(a)
Stability after one week in PBS
Total curcumin (mg)
Curcumincontent(mg)
0 2 4 6 8 10 12 14 16 18 20 22 24 26
0
1
2
3
4
5
6
7
After one week
Fresh
(b)
Figure 4: Stability test of curcumin/nanoparticle after one week at room temperature by DLS test.
(slightly higher concentration than CMC point; 0.03 mg/mL).
This low zeta-potential is at optimum range for stability of
PNPC and explains the reason of developing more uniform
size distribution (PdI = 0.182 ± 0.072) after one week at room
temperature [25, 26].
3.5. PNPC Encapsulation Efficiency and Drug Loading. The
average drug encapsulating efficiency and drug loading of
PNPC were 64 and 5.97 ± 2.1% (w/w), respectively. The
percentage of drug loading at different ratios of curcumin to
100 mg of nanocarrier was plotted in Figure 3. Curcumin did
not precipitate at 6% loading after 10 months of incubation
(Supplemental Figure 5).
3.6. PNPC Stability. PNPC was stable more than 300 days
at 4∘
C, although loading curcumin higher than 6% into
nanoparticles leads to some precipitation of curcumin (Sup-
plemental Figure 7). Lyophilized PNPC samples in water
dissolved by manual shaking without additional heating
or sonication. Then, size and distribution of PNP were
compared with freshly prepared PNPC by DLS (Fig-
ure 2(a)). After one week at 25∘
C, as mentioned, PNPC
samples inclined to develop more uniform polymersomes
nanoparticles (PdI = 0.182 ± 0.072). Furthermore, spec-
troscopy analysis showed that one-third of curcumin in
curcumin/nanocarriers micelles (pH = 7.2) was conserved at
room temperature after one week (Figure 4).
3.7. PNPC Effects on HuH-7 and 4T1 Cell Lines. PNPC
significantly suppressed the proliferation of HuH-7 and 4T1
cancerous cells in a dose- and time-dependent manner in
comparison with curcumin and PNP groups (𝑃 < 0.05).
7. BioMed Research International 7
0
20
40
60
80
100
120
140
0 10 20 30 40 50
PNPC
Curcumin
PNP
DOX
Concentration (𝜇M)
Cellviability(%)
4T1, 24h
(a)
0
20
40
60
80
100
120
0 10 20 30 40 50
PNPC
Curcumin
PNP
DOX
4T1, 48h
Concentration (𝜇M)
Cellviability(%)
(b)
0
20
40
60
80
100
120
0 20 40
Concentration (𝜇M)
PNPC Curcumin
DOXPNP
Cellviability(%)
HuH-7, 24h
(c)
0
20
40
60
80
100
120
0 10 20 30 40 50
PNPC
PNP
Curcumin
DOX
Concentration (𝜇M)
Cellviability(%)
HuH-7, 48h
(d)
Figure 5: Cytotoxic effects of PNPC on mouse mammary (4T1) and human hepatocellular (HuH-7) carcinoma cells. Cells were treated with
different concentrations of PNPC for 24 h (a) and 48 h (b) on 4T1 cell line and 24 h (c) and 48 h (d) on HuH-7 cell line. Data reported are
mean ± SD; ∗
𝑃 < 0.05 compared to curcumin; PNPC = the polymeric nanoparticle curcumin; PNP = polymeric nanoparticles.
PNPC IC50 for 4T1 cells was 29 𝜇M within 24 h (Figure 5(a)),
which relatively reduced to 24 𝜇M in 48 h (Figure 5(b)).
In addition, PNPC IC50 for HuH-7 cells was 25 𝜇M within
24 h (Figure 5(c)), which relatively reduced to 19 𝜇M in
48 h (Figure 5(d)). We showed concentration about 48 and
40 𝜇M for IC50 of free curcumin for 24 and 48 h, respectively.
Therefore, we showed that IC50 of the free curcumin is signifi-
cantly higher than PNPC, and PNPC significantly suppressed
cell growth compared to free curcumin (𝑃 < 0.05). In
addition, no significant toxicity was observed for void mPEG-
OA nanocarrier (PNP) even at concentrations above the
40 𝜇M. PNPC was not toxic to normal human fibroblastic
cells (HFSF-PI3) [13], and this data is in accordance with
other researcher results reviewed by Ravindran et al. [27].
PNPC showed nonsignificant changes in comparison with
the positive control group. PNPC and doxorubicin had no
effect on normal human fibroblasts cells (data not shown).
3.8. PNPC Toxicity. The main toxicity signs to PNPC and
PNP in various doses are summarized in Tables 1 and 2
and Supplemental Tables 1–5. In acute toxicity groups, doses
of 2000, 1000, 500, and 250 mg/kg of PNPC are associated
with death or severe poisoning symptoms. Additionally,
PNPC and PNP caused hematological, hepatocellular, and
renal toxicity at the acute dose of 125 mg/kg (Table 1 and
Supplemental Table 1). Higher doses provoked severe adverse
reactions and death especially at 250 mg/kg PNPC.
In the chronic toxicity groups, doses up to 62.5 mg/kg
PNPC brought about no death, but at 125 mg/kg PNPC, 2 out
of 6 mice died. Weight loss, diarrhea, imbalance, and ascites
were seen at 125 mg/kg of PNPC after one week of consecutive
injections. Survived animals (31.25 mg/kg and lower) had no
clinical differences compared with the control group. PNPC
showed remarkable safety rates up to 31.25 mg/kg (Tables 1
and 2 and Supplemental Tables 1 and 2).
8. 8 BioMed Research International
Table 1: Acute toxicity effects of PNPC on hematological and blood chemical indices in mice.
Parameters
Groups
Control PNPC
31.25 mg/kg
PNPC
62.5 mg/kg
PNPC
125 mg/kg
Animal weight (g) 24.3 ± 2.2 25 ± 3.1 24.7 ± 2.5 23.2 ± 2.2
RBC (Millin/mm3
) 6.08 ± 0.2 6.8 ± 0.8 7.2 ± 0.5 8.2 ± 0.4∗
HCT (%) 38.4 ± 1.7 37.7 ± 1.2 38.5 ± 2.5 42.5 ± 2∗
Hgb (g/dL) 10 ± 1.2 11.3 ± 1.8 11.7 ± 1.3 13.4 ± 1.6∗
MCV (FL) 51 ± 0.7 50.1 ± 0.8 49.3 ± 1.5 49.1 ± 1.2
MCH (pg) 16.5 ± 0.2 16.4 ± 0.3 15.5 ± 0.4 15.3 ± 0.3
MCHC (mol/L) 32.3 ± 0.7 32.4 ± 0.5 32.2 ± 0.4 32.5 ± 0.3
Plt (1000/mm3
) 567 ± 50 546 ± 91 570 ± 45 540 ± 38
WBC (1000/mm3
) 6.7 ± 0.8 8.7 ± 2 7.9 ± 1.5 8.1 ± 2.2
Neutrophils (%) 35.5 ± 2 36.6 ± 12 38 ± 5 38.2 ± 6
Monocytes (%) 2.1 ± 3 1.2 ± 0.9 3.1 ± 1 2.1 ± 0.8
Lymphocytes (%) 53.5 ± 6.4 52 ± 9 57.2 ± 5 57 ± 4
Na (mM/L) 150.3 ± 2.9 146.5 ± 3.3 154.2 ± 2.1 157.1 ± 1.5∗
K (mM/L) 5.2 ± 0.5 5.8 ± 1.3 6.1 ± 1.7 8.2 ± 2.2∗
Cl (mM/L) 111 ± 4 117 ± 3 114 ± 2 117 ± 3∗
HCO3−
(mM/L) 22.6 ± 3.2 17.3 ± 1.6 17.5 ± 2.2 16.3 ± 2.7∗
Osm (mOsm/kg) 307 ± 4.7 307 ± 5.2 312.2 ± 7 320 ± 8∗
Ca (mM/L) 0.72 ± 0.14 0.63 ± 0.1 0.65 ± 0.2 0.66 ± 0.3
Mg (mM/L) 0.29 ± 0.04 0.30 ± 0.03 0.25 ± 0.04 0.31 ± 0.03
Glu (mg/dL) 194 ± 33 204 ± 48 182 ± 30 176 ± 25
Lac (mM/L) 5.4 ± 1.2 5.2 ± 1.3 5.2 ± 2 5.7 ± 1.8
Urea (mg/dL) 21.2 ± 2.6 21.3 ± 3.6 26 ± 5 43 ± 7∗
Cr (mg/dL) 0.48 ± 0.08 0.51 ± 0.07 0.55 ± 0.07 0.92 ± 0.12∗
AST (U/L) 455 ± 45 538 ± 85 777 ± 80 1280 ± 152∗
ALT (U/L) 68 ± 8.8 70.6 ± 8.7 86 ± 21 258 ± 86∗
ALP (U/L) 763 ± 50 794 ± 67 825 ± 36 1187 ± 92∗
GGT (U/L) 5.5 ± 0.5 — — 6.2 ± 0.6
ALB (mg/dL) 3 ± 0.2 — — 2.8 ± 0.4
T.BIL (mg/dL) 0.5 ± 0.03 — — 0.47 ± 0.05
D.BIL (mg/dL) 0.35 ± 0.05 — — 0.32 ± 0.04
Values are means ± SEM. ∗
𝑃 < 0.05 compared to control. PNPC = the polymeric nanoparticle curcumin, RBC = red blood cell, HCT = hematocrit, MCV
= mean corpuscular volume, MCH = mean corpuscular hemoglobin, MCHC = mean corpuscular hemoglobin concentration, WBC = white blood cells, Plt
= platelets, Na = sodium, K = potassium, Cl = chloride, HCO3−
= bicarbonate, Osm = osmolarity, Ca = calcium, Mg = magnesium, Cr = creatinine, Lac =
lactate, Glu = glucose, AST = aspartate transaminase, ALT = alanine transaminase, ALP = alkaline phosphatase, GGT = gamma-glutamyl transpeptidase, ALB
= albumin, T.BIL = total bilirubin, and D.BIL = direct bilirubin.
Hematological markers were measured by a complete
blood count analysis. No inflammatory responses were seen
in acute and chronic toxicity groups since total leukocyte
counts remained within normal range (Tables 1 and 2 and
Supplemental Table 1). In addition, significant increases in
RBC, Hct, and Hgb were seen in acute 125 mg/kg PNPC
and chronic 62.5 mg/kg PNPC groups compared to control
animals (𝑃 < 0.05) (Table 1 and Supplemental Table 1).
Na, K, and Cl were also statistically escalated, while HCO3−
drastically decreased in acute 125 mg/kg PNPC (Table 1)
and chronic 62.5 mg/kg PNPC-treated mice compared with
control groups (𝑃 < 0.05) (Table 2).
Plasma BUN and Cr levels were measured for kidney
function assessment, while ALP, T.Bil, D.Bil, GGT, ALB, ALT,
and AST were done for liver function evaluation. BUN and
Cr were significantly higher in animals of acute 125 mg/kg
PNPC (Tables 1 and 2) and chronic 62.5 mg/kg PNPC groups,
compared to control animals (𝑃 < 0.05) (Table 2 and
Supplemental Table 2). Furthermore, liver function tests
showed drastic increases in AST, ALT, and ALP levels in acute
125 mg/kg PNPC group (Table 1 and Supplemental Table 1)
and chronic 62.5 mg/kg PNPC group (Table 2 and Supple-
mental Table 1) compared to control mice (𝑃 < 0.05). On the
other hand, albumin level significantly lowered at 62.5 mg/kg
9. BioMed Research International 9
Table 2: Chronic toxicity effects of PNPC on hematological and blood chemical indices and the organs weight percentage in mice.
Parameters
Groups
Control PNPC
15.63 mg/kg
PNPC
31.25 mg/kg
PNPC
62.5 mg/kg
Animal weight (g) 24.3 ± 2.2 24 ± 3.2 23.3 ± 3.4 18.3 ± 2.7∗
RBC (Millin/mm3
) 6.08 ± 0.08 6.3 ± 0.07 6.9 ± 0.3 7.7 ± 0.4∗
HCT (%) 38.4 ± 1.7 36.6 ± 2.1 37.4 ± 1.2 40.3 ± 3.2
Hgb (g/dL) 10 ± 1.2 12 ± 1.1 9.8 ± 0.9 12.3 ± 1
MCV (FL) 51 ± 0.7 52.8 ± 0.6 50.4 ± 2 49.5 ± 1.5
MCH (pg) 16.5 ± 0.2 17.3 ± 0.3 15.7 ± 0.9 15.6 ± 0.5
MCHC (mol/L) 32.3 ± 0.7 32.8 ± 0.4 32 ± 0.7 32.2 ± 0.6
Plt (1000/mm3
) 567 ± 50 519 ± 75 539 ± 53 594 ± 41
WBC (1000/mm3
) 6.7 ± 0.8 6.9 ± 1 6.5 ± 1.8 7.7 ± 2.1
Neutrophils (%) 32.5 ± 2 41 ± 8 38.5 ± 11 42 ± 9
Monocytes (%) 2.1 ± 3 4.4 ± 2.1 1.8 ± 1 3.8 ± 2.2
Lymphocytes (%) 66.5 ± 6.4 53 ± 11 60.8 ± 5.8 51 ± 13
Na (mM/L) 150.3 ± 2.9 149.7 ± 3.2 151.2 ± 3.8 157.4 ± 1.5∗
K (mM/L) 5.2 ± 0.5 5.7 ± 1.6 4.9 ± 0.4 4.3 ± 0.8
Cl (mM/L) 111 ± 4 112.2 ± 2.1 112.7 ± 1.8 115.5 ± 2.3
HCO3−
(mM/L) 22.6 ± 3.2 16.7 ± 4.9 19.9 ± 3.2 18.9 ± 2.7
Osm (mOsm/kg) 307 ± 4.7 301.3 ± 12 306.9 ± 8.2 315.8 ± 7
Ca (mM/L) 0.72 ± 0.14 0.61 ± 0.14 0.74 ± 0.07 0.97 ± 0.6
Mg (mM/L) 0.29 ± 0.04 0.30 ± 0.02 0.32 ± 0.04 0.35 ± 0.03
Glu (mg/dL) 194 ± 33 174 ± 31 172 ± 40 212 ± 30
Lac (mM/L) 5.4 ± 1.2 4.8 ± 1 5.1 ± 1.1 4.3 ± 1.5
Urea (mg/dL) 21.2 ± 2.6 19.4 ± 3.2 20 ± 2.6 24.5 ± 3.8
Cr (mg/dL) 0.48 ± 0.08 0.42 ± 0.05 0.53 ± 0.03 0.98 ± 0.08∗
AST (U/L) 455 ± 45 423 ± 64 503 ± 33 585 ± 36∗
ALT (U/L) 68 ± 8.8 72.3 ± 5.9 76.3 ± 12 92.3 ± 5∗
ALP (U/L) 763 ± 50 633 ± 83 666 ± 85 207 ± 23∗
GGT (U/L) 5.5 ± 0.5 — 5.9 ± 0.8 6.4 ± 1
ALB (mg/dL) 3 ± 0.2 — 3.4 ± 0.6 2.3 ± 0.3∗
T.BIL (mg/dL) 0.5 ± 0.03 — 0.47 ± 0.13 0.56 ± 0.1
D.BIL (mg/dL) 0.35 ± 0.05 — 0.38 ± 0.08 0.34 ± 0.05
% body weight
Heart 0.52 ± 0.06 0.47 ± 0.04
Liver 6.3 ± 0.35 4.2 ± 0.26∗
Spleen 0.43 ± 0.05 0.58 ± 0.07
Lung 0.73 ± 0.09 0.71 ± 0.07
Kidney 1.53 ± 0.15 1.46 ± 0.22
Brain 1.12 ± 0.11 1.19 ± 0.15
Values are means ± SEM. ∗
𝑃 < 0.05 compared to control. PNPC = the polymeric nanoparticle curcumin, RBC = red blood cell, HCT = hematocrit, MCV
= mean corpuscular volume, MCH = mean corpuscular hemoglobin, MCHC = mean corpuscular hemoglobin concentration, WBC = white blood cells, Plt
= platelets, Na = sodium, K = potassium, Cl = chloride, HCO3−
= bicarbonate, Osm = osmolarity, Ca = calcium, Mg = magnesium, Cr = creatinine, Lac =
lactate, Glu = glucose, AST = aspartate transaminase, ALT = alanine transaminase, ALP = alkaline phosphatase, GGT = gamma-glutamyl transpeptidase, ALB
= albumin, T.BIL = total bilirubin, and D.BIL = direct bilirubin.
in chronic PNPC group compared to control animals (Table 2
and Supplemental Table 2). Liver and kidney weights were
decreased but spleen weight increased in 125 mg/kg PNPC
and PNP groups compared to controls groups (Table 2). It
seems that the liver and the kidney were the target organs for
the polymeric carrier toxicity in high doses.
In this study, we also injected 31.25 mg/kg PNPC for 7
consecutive days and animals were euthanized at the end of
10. 10 BioMed Research International
(A) (a)
(B)
(C)
(b)
(c)
Figure 6: Light microscopic analysis of organs impressed from PNPC (125 mg/kg). Mild Kupffer cells hyperplasia and sinusoidal distention
in favor of congestion were seen in the liver tissue [(A) (20x), (a) (40x)]. Moderate congestion, sinusoidal dilatation with preserved white
lymphoid pulp was seen in the spleen tissue [(B) (20x), (b) (20x)]. The glomeruli were unremarkable but mild peritubular congestion and
proteinaceous cast formations were noted in some kidney tubules [(C) (20x), (c) (40x)].
2, 4, and 12 weeks. No adverse reactions observed in hemato-
logical, blood chemical, and histological examinations in this
protocol (Supplemental Table 3).
We also compromised the toxicity of PNPC and PNP
each other. In the acute toxicity, no significant difference
was observed in hematological and blood chemical exami-
nations in various doses of PNPC and PNP (Supplemental
Table 4). But in the chronic groups, high BUN and AST
levels and low albumin serum level were seen at 62.5 mg/kg
PNP group compared to PNPC animals (Supplemental
Table 5).
3.9. Histopathology Examinations. In order to obtain an
accurate diagnosis of PNPC and PNP toxicity on microscopic
levels, major organs were histopathologically evaluated.
Compared with control, animals treated with 125 mg/kg
PNPC and PNP developed slight abdominal ascites, kidney,
liver, and spleen congestion after one-week consecutive injec-
tions. AST, ALT, ALP, and GGT drastic increases in these
groups may be assumed as liver dysfunction. These changes
were also congruent with elevated renal biomarkers. In the
liver, mild Kupffer cells hyperplasia and sinusoidal distention
in favor of congestion were seen (Figure 6(A)). In addition,
11. BioMed Research International 11
we observed moderate congestion, sinusoidal dilatation with
preserved white lymphoid pulp in the spleen tissue (Fig-
ure 6(B)). In the kidney, the glomeruli were unremarkable
but mild peritubular congestion and proteinaceous cast
formations were noted in some tubules (Figure 6(C)). In all
of the histopathological examinations we observed minimal
hepatic and renal toxicity. No histological abnormality was
found in other major organs such as the brain, the heart, and
the lung. Additionally, no significant pathologic changes were
found in the major organs of animals treated with 31.25 mg/kg
PNPC and lower doses compared with the control group, so
31.25 mg/kg dose was ruled out as the toxic dose.
3.10. PNPC Protective Effects on Animal Breast Cancer. In the
protective study, PNPC was injected for 24 consecutive days,
from 3 days before to 21 days after tumor transplantation.
At the end of the study, the tumor take rate was at 37.5%
in comparison with control group (87.5%; 𝑃 < 0.05).
Additionally, PNPC-treated mice had a greater survival rate
of at least 20 weeks after tumor transplantation compared to
the control animals who died by the end of the eighth week.
3.11. PNPC Therapeutic Effects on Animal Breast Cancer.
PNPC was given for 24 days after tumor transplantation from
day 14 up to day 38 to evaluate the therapeutic effects of PNPC
on mice breast cancer. At the end of the third week, the tumor
disappeared in 3 and the tumor volume decreased in 3 and
increased in other two mice in PNPC group. Animals gained
weight in PNPC group compared to the negative control. The
average tumor volume and weight were significantly less than
the negative control in the second and third weeks after PNPC
treatment (𝑃 < 0.05). The mean final tumor volume reached
approximately 390 mm3
and 1420 mm3
in PNPC-treated and
control animals, respectively (Figure 7). The mean tumor
volume and weight in the positive control group showed
insignificant changes with PNPC group.
3.12. The Tumor Type and Characterization. Spontaneous
mouse mammary tumor was invasive ductal carcinoma,
malignant cells with hyperchromatic and polymorphism
nuclei, and a low to moderate rate of mitosis. Tumor cell
infiltration was observed in the surrounding tissues and nests
of carcinoma cells with grade II/III based on Scarff-Bloom-
Richardson Scale (Supplemental Figure 6).
3.13. Metastases. At the end of the study, all animals under-
went routine surgery. There were no signs of metastasis in
major organs of both PNPC-treated and control groups.
3.14. Immunohistochemistry Examinations. Immunohisto-
chemistry examinations in PNPC-treated animals showed
increased proapoptotic Bax protein expression in breast
tumor in comparison with control (Figure 8 and Supple-
mental Figure 7A). Antiapoptotic Bcl-2 protein expression
conceivably lowered after PNPC therapy (Figure 8 and
Supplemental Figure 7B). In addition, treatment with PNPC
caused a significant reduction in Bcl-2 activity and Bcl-2/Bax
ratio compared to the control group (𝑃 < 0.05).
0
0.5
1
1.5
2
14 21 28 35
Days
Negative control
Positive control
PNCP
∗∗
∗
∗
Meantumorsize(cm3
)
Figure 7: The polymeric nanoparticle curcumin effects on tumor
size (cm3
) in mouse mammary tumor. The positive control: “dox-
orubicin and cyclophosphamide were used as positive control.” Data
reported are mean ± SD; ∗
𝑃 < 0.05 compared to negative control;
PNPC = polymeric nanoparticle curcumin.
0
0.5
1
1.5
2
2.5
3
Bax Bcl-2 Ki67 CD31
Meanexpression
Parameters
Control
PNPC
∗∗∗
∗
Figure 8: The polymeric nanoparticle curcumin effects on immuno-
histochemical markers in mouse mammary tumor. Data reported
are mean ± SD; ∗
𝑃 < 0.05 compared to control; PNPC = polymeric
nanoparticle curcumin.
Angiogenesis also dramatically decreased in breast
tumors of PNPC-treated animals. CD31 activity reduced in
PNPC-treated mice tumors compared to control animals
(Figure 8 and Supplemental Figure 7C). Moreover, most of
the tumor cells represented high Ki67 marker in control
group. The mean proliferative cell number in PNPC-treated
mice was lower than the control group (𝑃 < 0.05) (Figure 8
and Supplemental Figure 7D).
4. Discussion
Our study showed that the polymeric nanocarrier is a
negative, amphipathic, and biodegradable polymer suitable
for drug delivery. They are new types of biocompatible
polymeric chains taken from plant fatty acids suitable for
curcumin bioavailability. Figure 1 shows that, with increasing
12. 12 BioMed Research International
nanocarrier concentration to more than CMC, the flores-
cence intensity has significantly risen. This is due to the self-
aggregation of micelle blocks and development of hydropho-
bic compartment inside the micelles and subsequent increase
of pyrene florescence. Additionally, CMC low value indicates
micelles thermodynamic stability which is enhanced after
extreme in vivo dilution and may improve circulation time
compared to surfactant micelles [14]. Another advantage of
this nanocarrier is its small size which provokes passive
targeting of the tumor tissues by increasing permeability and
retention. Moreover, the stability of encapsulated curcumin
in the polymeric nanoparticle is quite appropriate comparing
with free curcumin which degrades to about 90% after 30 min
[28]. Therefore, this nanocarrier conserves curcumin from
decomposition and degradation and can be considered as an
appropriate drug carrier for in vitro and in vivo experiments.
The major goal of our study was to develop polymeric
nanoparticle curcumin as an applicable strategy in can-
cer treatment. Toxicity is a crucial factor for nanoparticle
safety in nanomedicine arena. Understanding of various
determinants of nanoparticle toxicity helps establishing suit-
able strategies for selecting appropriate compositions to
develop biocompatible and efficacious polymeric carriers
in nanomedicine requests. In our study, the polymeric
nanoparticle curcumin significantly suppressed proliferation
of human and mouse carcinoma cells in vitro. Based on
hematological, blood chemical, and histopathological exam-
inations, minimal hepatic and renal toxicity was seen with
high PNPC doses. In addition, in vivo results showed that
tumor incidence, weight, and size were significantly declined
in PNPC-treated animals. PNPC also induced proapoptotic
Bax protein expression and reduced antiapoptotic Bcl-2
protein levels relative to the control group. Moreover, pro-
liferative and angiogenic markers were lowered in PNPC-
treated animals. These findings point to the features of the
polymeric carrier as a promising drug delivery system for
cancer therapy.
In the present study, we showed that monotherapy with
PNPC at high doses (250 mg/kg) and polymeric nanocarrier
alone caused the animal acute death. Daily administration of
PNPC and PNP at higher doses (125 mg/kg) for one week
has also been life-threatening. Macroscopic changes such
as ascites, weight loss, and imbalance together with other
untoward sequels like splenomegaly were also seen in some
animals. Histological examinations revealed macrophage
infiltration and splenic hyperplasia. Sodium and K+
levels
were significantly increased at high PNPC doses compared to
the control animals. This indicates that fluid balance is some-
how affected by PNPC administration and is in agreement
with ascites and diarrhea observed in some animals at the
same dose groups. RBC, Hct, and Hgb levels were drastically
increased at 62.5 mg/kg and higher doses compared to the
controls. Increased Cr level may be due to Cr release from
damaged muscular cells [21]. We are not sure about the
reversibility of PNPC and PNP induced blood chemistry
and hematological changes since it is beyond the scope of
the present study. Significant decrease in liver weight and
albumin level together with increased ALT, AST, ALP, and
GGT in PNPC- or PNP-treated animals points to the hepatic
effects of high doses and may by induced by polymeric
nanocarrier metabolism. Nevertheless, striking liver changes
on the above mentioned parameters were seen in animals
taking very high PNPC and PNP doses. These outcomes may
have been primary or secondary effects from nanocarrier in
some major organs such as liver, kidney, and spleen. Our
results support this hypothesis that mPEG may trigger liver
dysfunctions together with other organ toxicities [29, 30].
Our important finding is that the polymeric nanocarrier
dramatically increased tumor-suppressing effects of cur-
cumin both in cell culture and in a typical animal model of
breast cancer. Our results also showed that tumor incidence,
weight, and size were significantly declined in PNPC-treated
group. Fairly complete tumor regression after 24 days is a
dramatic finding with PNPC treatment observed in some
animals. We also observed a decrease in tumor incidence
as well as tumor size in both protective and PNPC-treated
mice compared to the control group. Tumor incidence
and size are indicators of proliferation and angiogenesis
[31]. Changes in tumor growth characteristics observed in
animals treated with PNPC suggest antiproliferative and
antiangiogenic effects of PNPC. Lower tumor incidence and
smaller tumor size may have been attributed to the direct
effects of PNPC owing to its potential antiproliferative and
antiangiogenic roles or its indirect strong oxidative response
[32]. It should be noted that other pathways involved in
the protective effects of PNPC are being pursued in our
laboratory.
Apoptosis role in breast carcinogenesis has been exten-
sively studied. It has been shown accordingly that resis-
tance to apoptosis in premalignant breast epithelial cells can
develop breast tumors [33]. In order to gain insight into
the mechanisms involved in apoptosis induction mediated
by PNPC in breast cancer, we studied its effects on the
expression of Bcl-2 and Bax proteins under in vivo situations.
Many genetic alterations of breast cancer are actually derived
from an imbalance between pro- and antiapoptotic members
of the Bcl-2 family [34]. It has generally been established
that oncoprotein Bcl-2 duels with its counteracting twin,
a protein known as Bax. Overexpression of Bax promotes
cell death; conversely, Bcl-2 functions as a suppressor of
apoptosis. A decrease in Bcl-2/Bax ratio has been considered
as a reliable indicator of the overall propensity of a cell to
undergo apoptosis [34]. In the present study, PNPC decreased
Bcl-2/Bax ratio by suppressing Bcl-2 expression and Bax
stimulation. This may be indicative of the Bcl-2 family role in
apoptosis induction mediated by PNPC in mice breast cancer
[35, 36]. These findings reveal a new therapeutic potential
for PNPC in different tissues malignancies via apoptosis
induction.
In addition, tumor growth noticeably depends on angio-
genesis where simultaneous enhances in the tumor vascula-
ture supply nutrients and oxygen to the growing neoplastic
cells is required [37]. Growth and progression of breast
tumor as well as growth of most of other cancers are
angiogenesis-dependent processes. High angiogenic activity
in the primary tumor seems to be well correlated with
untoward sequels in patients suffering from breast cancer.
Breast cancer is considered to be an angiogenic carcinoma
13. BioMed Research International 13
due to high expression of proangiogenic factors [38]. We
found in vivo anticarcinogenic properties of nanocurcumin
as effective as in vitro antiproliferative and antiangiogenic
effects of curcumin. These compounds presumably change
the balance of pro-and antiangiogenic factors in tumor tissues
and fix the effective delivery system of therapeutic drugs to
tumor cells in a larger scale. Our results provide support for
a potential therapeutic role of PNPC in breast cancer via
their antiangiogenic and antiproliferative properties. In fact,
it seems that the polymeric nanocarrier increases tumor cell
access to curcumin and in turn, it causes tumor cells death.
In some previous reports, polymeric nanocarriers were
used for curcumin tissue delivery. Bisht et al. (2007) syn-
thesized a polymeric nanoparticle of curcumin (50–100 nm
range) in an encapsulated formulation utilizing micellar
aggregates of cross-linked and indiscriminate acrylic copoly-
mers of N-isopropylacrylamide (NIPAAM) with N-vinyl-2-
pyrrolidone (VP) [15]. An ideal drug delivery platform must
be biodegradable, biocompatible, and free from incidental
adverse effects. Bisht’s nanocarriers are nondegradable and
harmful to health due to NIPAAM, VP, and poly(ethylene
glycol) monoacrylate monomers use. But, in our nanocarrier
form, fatty acids with biodegradable and biocompatible
properties were adopted to produce the least health harmful
effects unless in very high doses. In addition, Anand et
al. (2010) used PLGA-poly-ethylene glycol nanoparticles to
deliver encapsulated curcumin with 97.5% efficiency but
low drug loading [39]. Our data reveals for the first time
that nanopolymeric compounds not only boost curcumin
solubility and uptake in cell lines but also increase its toxicity
on cancer cells. This issue with the biodegradable ability
shows that polymeric carriers are unique host cell drug in
animal models as per the following aspects.
(a) They are inexpensive, neutral, nontoxic, biodegrad-
able, and easy to use.
(b) Pharmaceutical agents can create a weak structural
combination helping their easy cellular separation.
(c) Although nanocarriers are biodegradable, they are
stable and resistant not only in dry environments but
also in fluids with low temperature.
5. Conclusion
In summary, we showed that PNPC is effective in sup-
pressing tumor growth both in vitro and in vivo. Tumor
growth in PNPC-treated mice was significantly suppressed
and/or almost completely stopped at the end of the treat-
ment. Our results also suggested PNPC appropriate dose
(31.25 mg/kg/daily for 3 weeks). Lower doses effectiveness or
fewer PNPC shots are currently being investigated in our
laboratory. The present study provides persuasive evidence
for polymeric nanocarrier superior biocompatibility in phar-
macological arena which in turn can reduce anticancer drug
side effects with excellent tumor-suppressing response.
Conflict of Interests
The authors reported no conflict of interests. The authors
alone are responsible for the content of the paper.
Acknowledgment
This study was supported by a grant of Tehran University of
Medical Sciences.
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