Paclitaxel is an effective chemotherapy drug used to treat cancers like lung, breast, and ovarian cancer. However, it has poor water solubility requiring formulation with Cremophor EL, which can cause hypersensitivity reactions. Nanoparticle formulations have been developed to improve delivery of Paclitaxel, including Abraxane which uses albumin nanoparticles to deliver the drug and reduce side effects compared to Cremophor EL formulations. Abraxane transports Paclitaxel into tumors by binding to albumin receptors on endothelial cells or through overexpression of SPARC protein in many tumor types. New prodrug formulations and nanoparticle delivery systems aim to improve the solubility, stability, and targeting of Pacl
Paclitaxel is a chemotherapy drug that was originally isolated from the bark of the Pacific yew tree. It works by inhibiting cell division through binding to microtubules and preventing depolymerization. Common side effects include neutropenia and peripheral neuropathy. Paclitaxel has been clinically used to treat various cancers like lung cancer and breast cancer. While an effective drug, production from natural sources is challenging due to low yields, leading to development of semi-synthetic and recombinant techniques for production.
The document summarizes research on the preparation and characterization of paclitaxel-loaded poly-L-co-D,L-lactic acid (PLDLA) microspheres for use as a drug delivery system. PLDLA microspheres were produced using an emulsion technique and characterized. The average size of microspheres with and without paclitaxel was approximately 10-13 micrometers. Differential scanning calorimetry showed that paclitaxel was homogeneously dispersed within the amorphous PLDLA microspheres rather than crystallized. The encapsulation efficiency of paclitaxel in the PLDLA microspheres was 98%. In vitro drug release studies
This document provides a comprehensive review of nanoparticle delivery systems for paclitaxel (PX), an effective but toxic chemotherapy drug. It discusses the limitations of the standard PX formulation using Cremophor EL and ethanol. Nanoparticle delivery can overcome these issues by improving PX's solubility, pharmacokinetics, and targeting to tumors while reducing toxicity. The review covers many PX nanoparticle formulations including polymeric nanoparticles (especially PLGA), lipid-based nanoparticles, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. It finds that these systems enhance PX's efficacy against cancer cells in vitro and tumor growth inhibition in vivo compared to free P
Rational drug design begins by identifying a biological target implicated in disease. Drugs are then designed to modulate this target's activity in order to treat the disease. For a target to be suitable, there must be evidence it is disease-relevant and capable of binding small molecules. Once identified, the target is cloned, expressed, and purified. This allows high-throughput screening of chemical libraries to identify candidates that modify the target. Successful candidates should have properties predicting oral availability and low toxicity. Prodrugs and combinatorial chemistry are approaches that can improve drug properties and efficiency of discovery.
This document summarizes several classes of anticancer drugs, including taxanes like paclitaxel and docetaxel, and podophyllotoxins like etoposide and teniposide. It notes the limitations of paclitaxel including its poor solubility and limited supply, and how docetaxel was developed to address these issues. The document also discusses the biosynthesis of paclitaxel from precursors like baccatin III, as well as podophyllotoxin derivatives and their mechanisms of inhibiting DNA synthesis.
1. The document describes a study on using vitamin E TPGS-emulsified PLGA nanoparticles as carriers for delivering paclitaxel to treat cardiovascular restenosis.
2. The nanoparticles were characterized and found to have higher drug encapsulation efficiency and cytotoxicity compared to PVA-emulsified nanoparticles in cellular studies.
3. The TPGS-emulsified PLGA nanoparticles showed potential for effective and sustainable delivery of antiproliferative drugs for developing nanoparticle-coated cardiovascular stents to prevent restenosis.
Paclitaxel is a chemotherapy drug that was originally isolated from the bark of the Pacific yew tree. It works by inhibiting cell division through binding to microtubules and preventing depolymerization. Common side effects include neutropenia and peripheral neuropathy. Paclitaxel has been clinically used to treat various cancers like lung cancer and breast cancer. While an effective drug, production from natural sources is challenging due to low yields, leading to development of semi-synthetic and recombinant techniques for production.
The document summarizes research on the preparation and characterization of paclitaxel-loaded poly-L-co-D,L-lactic acid (PLDLA) microspheres for use as a drug delivery system. PLDLA microspheres were produced using an emulsion technique and characterized. The average size of microspheres with and without paclitaxel was approximately 10-13 micrometers. Differential scanning calorimetry showed that paclitaxel was homogeneously dispersed within the amorphous PLDLA microspheres rather than crystallized. The encapsulation efficiency of paclitaxel in the PLDLA microspheres was 98%. In vitro drug release studies
This document provides a comprehensive review of nanoparticle delivery systems for paclitaxel (PX), an effective but toxic chemotherapy drug. It discusses the limitations of the standard PX formulation using Cremophor EL and ethanol. Nanoparticle delivery can overcome these issues by improving PX's solubility, pharmacokinetics, and targeting to tumors while reducing toxicity. The review covers many PX nanoparticle formulations including polymeric nanoparticles (especially PLGA), lipid-based nanoparticles, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. It finds that these systems enhance PX's efficacy against cancer cells in vitro and tumor growth inhibition in vivo compared to free P
Rational drug design begins by identifying a biological target implicated in disease. Drugs are then designed to modulate this target's activity in order to treat the disease. For a target to be suitable, there must be evidence it is disease-relevant and capable of binding small molecules. Once identified, the target is cloned, expressed, and purified. This allows high-throughput screening of chemical libraries to identify candidates that modify the target. Successful candidates should have properties predicting oral availability and low toxicity. Prodrugs and combinatorial chemistry are approaches that can improve drug properties and efficiency of discovery.
This document summarizes several classes of anticancer drugs, including taxanes like paclitaxel and docetaxel, and podophyllotoxins like etoposide and teniposide. It notes the limitations of paclitaxel including its poor solubility and limited supply, and how docetaxel was developed to address these issues. The document also discusses the biosynthesis of paclitaxel from precursors like baccatin III, as well as podophyllotoxin derivatives and their mechanisms of inhibiting DNA synthesis.
1. The document describes a study on using vitamin E TPGS-emulsified PLGA nanoparticles as carriers for delivering paclitaxel to treat cardiovascular restenosis.
2. The nanoparticles were characterized and found to have higher drug encapsulation efficiency and cytotoxicity compared to PVA-emulsified nanoparticles in cellular studies.
3. The TPGS-emulsified PLGA nanoparticles showed potential for effective and sustainable delivery of antiproliferative drugs for developing nanoparticle-coated cardiovascular stents to prevent restenosis.
The document summarizes a presentation on developing paclitaxel nanoparticles using human serum albumin (HSA) as a polymer. Paclitaxel is insoluble in water and has low bioavailability. Nanoparticles can increase paclitaxel's stability, target delivery to tumor sites, and reduce toxicity. The method involves dissolving paclitaxel in chloroform and mixing it with an HSA solution to form an emulsion. The chloroform is then evaporated to form paclitaxel-loaded HSA nanoparticles.
In vitro and in vivo evaluation of positively charged liposaccharide derivati...Adel Abdelrahim, PhD
This document describes a study evaluating positively charged liposaccharide derivatives as oral absorption enhancers for delivering anionic drugs. Positively charged liposaccharide derivatives were synthesized and combined with the anionic model drug piperacillin through ion pairing. The conjugates were evaluated in vitro and in vivo to assess antimicrobial activity, plasma stability, permeability across Caco-2 cell monolayers, and oral absorption. Results showed that ion pairing the liposaccharide derivatives with piperacillin improved permeability in Caco-2 cells without altering antimicrobial activity, indicating potential as oral absorption enhancers.
Antimicrotubule agents such as paclitaxel and docetaxel are microtubule-stabilizing drugs that directly bind to tubulin. They profoundly alter microtubule dynamics and suppress microtubule depolymerization, leading to mitotic arrest. Peripheral neuropathy is a common side effect due to their effects on microtubules in neurons. Paclitaxel and docetaxel are effective in treating several types of cancer but require premedication to reduce hypersensitivity reactions and have dose-limiting toxicities of neutropenia and neuropathy.
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.
Dosage forms refer to how pharmaceutical drugs are marketed and administered to patients. They include capsules, tablets, suppositories, and ointments. Capsules contain medications enclosed in a shell, while tablets are solid compressed doses that may contain one or more active ingredients. Suppositories are solid forms inserted into orifices to exert local or systemic effects. Ointments are viscous preparations used topically. Drug delivery aims to transport pharmaceutical compounds safely in the body to achieve their therapeutic effects and includes approaches like targeted delivery, sustained release formulations, and protecting oral drugs from stomach acid.
The document discusses natural products taxanes and podophyllotoxins that have led to new anti-cancer drugs. It describes how over 60% of anti-cancer drugs originate from natural products. Taxanes such as paclitaxel and docetaxel stabilize microtubules, preventing cell division and causing cancer cell death. Podophyllotoxins like etoposide and teniposide inhibit topoisomerase and DNA synthesis in cancer cells. Both classes are effective against various cancer types with side effects like low blood counts and hair loss that require careful treatment. Natural products continue providing leads for developing new anti-cancer pharmaceuticals.
This document provides information about paclitaxel nanoparticles, including:
1. It introduces paclitaxel and human serum albumin, which are used to develop paclitaxel nanoparticles.
2. The method of preparing paclitaxel nanoparticles involves mixing paclitaxel, chloroform, and a 25% human serum albumin solution to form nanoparticles.
3. The document provides details on the drug and polymer profiles, including properties, storage conditions, and clinical uses of paclitaxel and human serum albumin.
This document discusses polysaccharides as building blocks for nanotherapeutics in drug delivery. It defines different types of carbohydrates like monosaccharides, oligosaccharides, and polysaccharides. It then classifies polysaccharides based on their origin as plant, animal, algal, microbial, or marine. Polysaccharides are also classified based on their monomer units as homo- or heteropolysaccharides. Examples of specific polysaccharides like starch, cellulose, chitosan, hyaluronic acid, dextran, and cyclodextrins are provided along with their properties and applications. Requirements for efficient drug delivery vehicles and important drug delivery systems are also summarized. The document concludes that polysaccharide nanop
The document summarizes the formulation and evaluation of liposomal drug delivery systems for the anticancer drug docetaxel. Liposomes were prepared using the thin film hydration method with soybean lecithin and cholesterol. Preformulation studies such as FTIR spectroscopy confirmed no chemical interactions between docetaxel and the lipid components. The liposomes were characterized for particle size, zeta potential, and in vitro drug release kinetics. Short term stability studies were also planned to evaluate the stability of the liposomal formulations. The goal was to reduce the side effects of docetaxel and improve its targeting to tumor sites.
Adeeva Life Care Pvt. Ltd. is setup by KPS Clinical Services Pvt. Ltd. (a leading Contract Research Organization) in the auspicious of RAHE Group of Organizations.
Adeeva Life Care is a different kind of pharmaceutical and healthcare products company. We are an India based company focused on management of various kinds of ailments by developing our unique range of innovative products.
Several Types of PROTACs Based On Nucleic AcidsDoriaFang
So far, more than 10 nucleic acid drugs have been approved for marketing worldwide, and many nucleic acid drugs are in the stage of clinical trials. Nucleic acid drugs are expected to become the third type of drugs after small molecule drugs and antibody drugs.
The document discusses body fluid compartments and their compositions. It notes that total body water makes up 60% of body weight, with two thirds located intracellularly and one third extracellularly. The extracellular fluid consists of interstitial fluid and blood plasma. Key electrolytes like sodium, potassium, calcium, and chloride are discussed along with their concentrations in plasma, interstitial, and intracellular fluids. Various volume expanders used to increase blood volume are also described, including crystalloids like saline and lactated Ringer's, as well as colloids like albumin, dextrans, gelatin, hydroxyethyl starch, and polyvinylpyrrolidone. Their mechanisms of action, properties, uses,
This document discusses several potential drug-drug interactions involving various medications:
1. A woman taking simvastatin, diltiazem, aspirin is prescribed clarithromycin. Clarithromycin is a strong CYP3A4 inhibitor and may significantly increase simvastatin levels, increasing risk of side effects like rhabdomyolysis. The patient's simvastatin dose should not exceed 40 mg daily while taking clarithromycin.
2. Minocycline is unlikely to reduce the effectiveness of a low-dose combined oral contraceptive. Any interaction would be due to suppressed gut bacteria and is considered very rare.
3. A man's phenytoin levels increased after starting flu
This document summarizes key information about several classes of antibiotics - tetracyclines, aminoglycosides, macrolides, and chloramphenicol. It describes their mechanisms of action, which involve inhibiting bacterial protein synthesis or damaging cell membranes. It also outlines their structure-activity relationships, common uses for treating bacterial infections, potential adverse effects like nephrotoxicity and ototoxicity, and dosing information. The document appears to be from a presentation on different antibiotic classes for educational purposes.
MOLECULAR MECHANISMS OF FDA APPROVED DRUGS IN 2014jose_pharma
This document summarizes 19 drugs approved by the FDA in 2014. It provides the drug name, company, approved indication, and molecular mechanism of action for each drug in 1-2 sentences. The drugs cover a wide range of therapeutic areas and include small molecule drugs, biologics, and vaccines.
A tyrosine kinase is an enzyme that transfers a phosphate group from ATP to tyrosine residues on proteins. This phosphorylation regulates protein activity and signal transduction within cells. Tyrosine kinase inhibitors, like nilotinib, are drugs that bind to and inhibit tyrosine kinases. Nilotinib was approved to treat chronic myeloid leukemia and research found it was effective against drug-resistant forms of the disease. It works by binding the inactive form of the Abl kinase to prevent phosphorylation and cancer cell growth.
This document is a letter informing the author that changes made to the HTML version of their article will be added before publication but are not reflected in the attached PDF file. The letter also notes that the PDF should not be used for submitting corrections. The PDF then contains a research article examining the structure-activity relationships of redox active thiol peroxidase mimic compounds. The study relates the ability of organoselenium and organotellurium compounds to catalyze the oxidation of glutathione and dihydrolipoic acid to their cytotoxicity and ability to act as antioxidants or prooxidants in cancer cells. The results show dihydrolipoic acid oxidation correlates with cytotoxicity and prooxidant action, allowing prediction of compound
Clopidogrel is a prodrug used to inhibit platelet aggregation. It requires hepatic metabolism to form its active metabolite. The metabolite binds irreversibly to the P2Y12 receptor on platelets to inhibit ADP-induced platelet activation and aggregation. Pharmacokinetic studies have found challenges in measuring clopidogrel and its active metabolite due to their instability and low plasma concentrations. Genetic polymorphisms of CYP enzymes involved in clopidogrel metabolism can affect its activation and antiplatelet effects.
Formulation development and evalution of matrix tablet ofGajanan Ingole
The document describes the development of a matrix tablet for oral delivery of an antihypertensive drug (NSL) using pH dependent and independent polymers. It includes sections on introduction, literature review, drug and excipient profiles, aim and objectives, rationale, materials and equipment, experimental work, results, discussion, and references. The key steps involved preformulation studies, formulation of matrix tablets, optimization studies to match the in vitro dissolution profile of a marketed reference product, and stability studies. The optimized formulation was found to release the drug in a controlled manner for 24 hours.
This week we are going to participate in a.docxwrite5
This week students will participate in a debate on whether the French Revolution was worth its human cost. They will be split into two groups - one arguing yes and one arguing no. The group arguing yes will analyze an excerpt from Peter Kropotkin's book The Great French Revolution 1789-1793 to defend their position that the French Revolution was worth its significant human toll.
This week begins an overview of the Research In.docxwrite5
This document provides an overview of the research process for an academic paper. It discusses considering thesis, motive, structure, finding topics, audience, and structuring the argument with initial research. The document recommends reviewing a guide to the elements of academic writing and lists three online writing support resources as samples for additional academic support.
The document summarizes a presentation on developing paclitaxel nanoparticles using human serum albumin (HSA) as a polymer. Paclitaxel is insoluble in water and has low bioavailability. Nanoparticles can increase paclitaxel's stability, target delivery to tumor sites, and reduce toxicity. The method involves dissolving paclitaxel in chloroform and mixing it with an HSA solution to form an emulsion. The chloroform is then evaporated to form paclitaxel-loaded HSA nanoparticles.
In vitro and in vivo evaluation of positively charged liposaccharide derivati...Adel Abdelrahim, PhD
This document describes a study evaluating positively charged liposaccharide derivatives as oral absorption enhancers for delivering anionic drugs. Positively charged liposaccharide derivatives were synthesized and combined with the anionic model drug piperacillin through ion pairing. The conjugates were evaluated in vitro and in vivo to assess antimicrobial activity, plasma stability, permeability across Caco-2 cell monolayers, and oral absorption. Results showed that ion pairing the liposaccharide derivatives with piperacillin improved permeability in Caco-2 cells without altering antimicrobial activity, indicating potential as oral absorption enhancers.
Antimicrotubule agents such as paclitaxel and docetaxel are microtubule-stabilizing drugs that directly bind to tubulin. They profoundly alter microtubule dynamics and suppress microtubule depolymerization, leading to mitotic arrest. Peripheral neuropathy is a common side effect due to their effects on microtubules in neurons. Paclitaxel and docetaxel are effective in treating several types of cancer but require premedication to reduce hypersensitivity reactions and have dose-limiting toxicities of neutropenia and neuropathy.
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.
Dosage forms refer to how pharmaceutical drugs are marketed and administered to patients. They include capsules, tablets, suppositories, and ointments. Capsules contain medications enclosed in a shell, while tablets are solid compressed doses that may contain one or more active ingredients. Suppositories are solid forms inserted into orifices to exert local or systemic effects. Ointments are viscous preparations used topically. Drug delivery aims to transport pharmaceutical compounds safely in the body to achieve their therapeutic effects and includes approaches like targeted delivery, sustained release formulations, and protecting oral drugs from stomach acid.
The document discusses natural products taxanes and podophyllotoxins that have led to new anti-cancer drugs. It describes how over 60% of anti-cancer drugs originate from natural products. Taxanes such as paclitaxel and docetaxel stabilize microtubules, preventing cell division and causing cancer cell death. Podophyllotoxins like etoposide and teniposide inhibit topoisomerase and DNA synthesis in cancer cells. Both classes are effective against various cancer types with side effects like low blood counts and hair loss that require careful treatment. Natural products continue providing leads for developing new anti-cancer pharmaceuticals.
This document provides information about paclitaxel nanoparticles, including:
1. It introduces paclitaxel and human serum albumin, which are used to develop paclitaxel nanoparticles.
2. The method of preparing paclitaxel nanoparticles involves mixing paclitaxel, chloroform, and a 25% human serum albumin solution to form nanoparticles.
3. The document provides details on the drug and polymer profiles, including properties, storage conditions, and clinical uses of paclitaxel and human serum albumin.
This document discusses polysaccharides as building blocks for nanotherapeutics in drug delivery. It defines different types of carbohydrates like monosaccharides, oligosaccharides, and polysaccharides. It then classifies polysaccharides based on their origin as plant, animal, algal, microbial, or marine. Polysaccharides are also classified based on their monomer units as homo- or heteropolysaccharides. Examples of specific polysaccharides like starch, cellulose, chitosan, hyaluronic acid, dextran, and cyclodextrins are provided along with their properties and applications. Requirements for efficient drug delivery vehicles and important drug delivery systems are also summarized. The document concludes that polysaccharide nanop
The document summarizes the formulation and evaluation of liposomal drug delivery systems for the anticancer drug docetaxel. Liposomes were prepared using the thin film hydration method with soybean lecithin and cholesterol. Preformulation studies such as FTIR spectroscopy confirmed no chemical interactions between docetaxel and the lipid components. The liposomes were characterized for particle size, zeta potential, and in vitro drug release kinetics. Short term stability studies were also planned to evaluate the stability of the liposomal formulations. The goal was to reduce the side effects of docetaxel and improve its targeting to tumor sites.
Adeeva Life Care Pvt. Ltd. is setup by KPS Clinical Services Pvt. Ltd. (a leading Contract Research Organization) in the auspicious of RAHE Group of Organizations.
Adeeva Life Care is a different kind of pharmaceutical and healthcare products company. We are an India based company focused on management of various kinds of ailments by developing our unique range of innovative products.
Several Types of PROTACs Based On Nucleic AcidsDoriaFang
So far, more than 10 nucleic acid drugs have been approved for marketing worldwide, and many nucleic acid drugs are in the stage of clinical trials. Nucleic acid drugs are expected to become the third type of drugs after small molecule drugs and antibody drugs.
The document discusses body fluid compartments and their compositions. It notes that total body water makes up 60% of body weight, with two thirds located intracellularly and one third extracellularly. The extracellular fluid consists of interstitial fluid and blood plasma. Key electrolytes like sodium, potassium, calcium, and chloride are discussed along with their concentrations in plasma, interstitial, and intracellular fluids. Various volume expanders used to increase blood volume are also described, including crystalloids like saline and lactated Ringer's, as well as colloids like albumin, dextrans, gelatin, hydroxyethyl starch, and polyvinylpyrrolidone. Their mechanisms of action, properties, uses,
This document discusses several potential drug-drug interactions involving various medications:
1. A woman taking simvastatin, diltiazem, aspirin is prescribed clarithromycin. Clarithromycin is a strong CYP3A4 inhibitor and may significantly increase simvastatin levels, increasing risk of side effects like rhabdomyolysis. The patient's simvastatin dose should not exceed 40 mg daily while taking clarithromycin.
2. Minocycline is unlikely to reduce the effectiveness of a low-dose combined oral contraceptive. Any interaction would be due to suppressed gut bacteria and is considered very rare.
3. A man's phenytoin levels increased after starting flu
This document summarizes key information about several classes of antibiotics - tetracyclines, aminoglycosides, macrolides, and chloramphenicol. It describes their mechanisms of action, which involve inhibiting bacterial protein synthesis or damaging cell membranes. It also outlines their structure-activity relationships, common uses for treating bacterial infections, potential adverse effects like nephrotoxicity and ototoxicity, and dosing information. The document appears to be from a presentation on different antibiotic classes for educational purposes.
MOLECULAR MECHANISMS OF FDA APPROVED DRUGS IN 2014jose_pharma
This document summarizes 19 drugs approved by the FDA in 2014. It provides the drug name, company, approved indication, and molecular mechanism of action for each drug in 1-2 sentences. The drugs cover a wide range of therapeutic areas and include small molecule drugs, biologics, and vaccines.
A tyrosine kinase is an enzyme that transfers a phosphate group from ATP to tyrosine residues on proteins. This phosphorylation regulates protein activity and signal transduction within cells. Tyrosine kinase inhibitors, like nilotinib, are drugs that bind to and inhibit tyrosine kinases. Nilotinib was approved to treat chronic myeloid leukemia and research found it was effective against drug-resistant forms of the disease. It works by binding the inactive form of the Abl kinase to prevent phosphorylation and cancer cell growth.
This document is a letter informing the author that changes made to the HTML version of their article will be added before publication but are not reflected in the attached PDF file. The letter also notes that the PDF should not be used for submitting corrections. The PDF then contains a research article examining the structure-activity relationships of redox active thiol peroxidase mimic compounds. The study relates the ability of organoselenium and organotellurium compounds to catalyze the oxidation of glutathione and dihydrolipoic acid to their cytotoxicity and ability to act as antioxidants or prooxidants in cancer cells. The results show dihydrolipoic acid oxidation correlates with cytotoxicity and prooxidant action, allowing prediction of compound
Clopidogrel is a prodrug used to inhibit platelet aggregation. It requires hepatic metabolism to form its active metabolite. The metabolite binds irreversibly to the P2Y12 receptor on platelets to inhibit ADP-induced platelet activation and aggregation. Pharmacokinetic studies have found challenges in measuring clopidogrel and its active metabolite due to their instability and low plasma concentrations. Genetic polymorphisms of CYP enzymes involved in clopidogrel metabolism can affect its activation and antiplatelet effects.
Formulation development and evalution of matrix tablet ofGajanan Ingole
The document describes the development of a matrix tablet for oral delivery of an antihypertensive drug (NSL) using pH dependent and independent polymers. It includes sections on introduction, literature review, drug and excipient profiles, aim and objectives, rationale, materials and equipment, experimental work, results, discussion, and references. The key steps involved preformulation studies, formulation of matrix tablets, optimization studies to match the in vitro dissolution profile of a marketed reference product, and stability studies. The optimized formulation was found to release the drug in a controlled manner for 24 hours.
This week we are going to participate in a.docxwrite5
This week students will participate in a debate on whether the French Revolution was worth its human cost. They will be split into two groups - one arguing yes and one arguing no. The group arguing yes will analyze an excerpt from Peter Kropotkin's book The Great French Revolution 1789-1793 to defend their position that the French Revolution was worth its significant human toll.
This week begins an overview of the Research In.docxwrite5
This document provides an overview of the research process for an academic paper. It discusses considering thesis, motive, structure, finding topics, audience, and structuring the argument with initial research. The document recommends reviewing a guide to the elements of academic writing and lists three online writing support resources as samples for additional academic support.
This week you are exploring what it means to have.docxwrite5
This week students are exploring the concept of privilege in different aspects of life. Having privilege means having some form of power through access to goods, services, education, or other resources. Those with privilege may not be aware of how they benefit from it. The document instructs students to complete a chart about their membership in dominant or subordinate groups, and to write a response addressing how privilege has shaped their life opportunities and experiences. They are asked to consider forms of privilege like race, socioeconomic status, and education.
Watch the TED Talk for Chapter 8 on Pay.docxwrite5
The document summarizes a TED Talk video about IQ and different types of intelligence. It asks the viewer to pay close attention to how the speaker defines IQ and also discusses other forms of intelligence. It prompts the viewer to consider how their own definition of intelligence compares to what was presented in the video, and whether research supports the claims made in the talk. It provides a link to the TED Talk video and instructs the viewer to write an initial post of at least 200 words discussing these topics and including a scholarly reference.
The value of diversity in groups and society is continually.docxwrite5
Diversity in groups and organizations is often debated, as it can provide both benefits and challenges, especially in the workplace where diversity awareness has changed how companies operate. Having diversity of things like background, experience and thought can strengthen a group by bringing different perspectives and ideas, though managing diversity also has complications. Diverse work teams can foster innovation but may also face communication difficulties.
The prompt analyzes The Travels of Sir John Mandeville, a 14th century account of the author's purported journeys around the world. It examines how Mandeville conceptualized and structured his depiction of the world, how he connected different peoples and cultures, and what criteria he used to determine inclusion and exclusion in his narrative. The prompt also considers how Mandeville's work relates to and expands upon previous historical accounts, and how his portrayal of non-European cultures fits into discussions about the inherent Eurocentrism of Western thinking. Students are asked to analyze Mandeville's text as a piece of primary evidence that provides insight into late medieval European perspectives on self and other.
This will enable you to understanding the extent to which.docxwrite5
This document discusses how social media companies have integrated into people's lives through collecting and commodifying personal user data. While Americans value privacy and freedom, technology has made these increasingly illusive as users are under surveillance through the technologies they use everyday. The document asks to identify reasons for changing attitudes about privacy invasion and discuss how awareness of surveillance affects personal behavior.
The Superfund website will have information about contaminated how.docxwrite5
The Superfund website provides information about contaminated areas, how they became polluted, and who is responsible for cleaning them up. It details the issue of contamination, the stakeholders involved including those responsible and impacted, and the effects on the local environment from specific contaminated sites. Clean-up plans are also outlined on the site.
The Strengths and Weaknesses of the North and South in.docxwrite5
The document examines the strengths and weaknesses of the North and South as they faced each other in 1861 at the outset of the Civil War. It discusses their differing political ideologies as seen in Abraham Lincoln and Jefferson Davis' leadership and speeches. The South relied on its powerful economic interest in slavery and sought to expand and protect it, while the North aimed to restrict slavery's territorial growth. Neither side anticipated the magnitude and duration of the conflict that ensued or that the war might end before the cause of the conflict.
This assignment will help you to explain the concept of.docxwrite5
This assignment asks students to research and analyze a domestic terrorist group by identifying its characteristics such as age, ethnicity and origins; explaining its ideological drivers and recruitment strategies; and discussing the challenges it poses to law enforcement. Students are to summarize their findings relating it to one theory and two relevant concepts or definitions from their research.
The Institutional Structure of the Communist.docxwrite5
The document outlines the topics and required readings for a course on the institutional structure of the Chinese Communist Party-state. The course covers topics such as the role of the CCP in the political system and how it stabilizes authoritarian rule, the fragmented nature of the Chinese state and the benefits and challenges it poses, central-local relations and why local governments may disobey central commands, the functions of legal institutions and the prospects for rule of law in China, the relationship between the government and private sector capitalists, the emergence of civil society, and the possibility for social unrest and common protest tactics.
The next couple of weeks begins an overview of the.docxwrite5
The document provides an overview of the upcoming weeks which will focus on research writing. It discusses considering elements like thesis, motive, structure, finding topics, and audience when developing an argument. Students are directed to additional resources for guidance on the academic writing process, including samples from Towson Online Writing Support, Purdue Online Writing Lab, and Excelsior Online Writing Lab.
Two general technology trends in my workplace are that EHRs.docxwrite5
Two technology trends in the workplace are increasing use of complex electronic health records (EHRs) and patients using smartphone apps for healthcare. The author discusses their experience transitioning between two EHRs - AURA which was less sophisticated, and EPIC which is more complex but customizable and allows greater communication between providers. Another trend is greater integration of devices and artificial intelligence into EHRs for automated data entry. However, overreliance on technology could replace sound clinical judgment, so nurses must use technology as a tool rather than a replacement for care. Patients are also increasingly using the internet and health apps, so providers should guide patients to evaluate online information for accuracy.
Two of the religions that we have studied in the.docxwrite5
This document asks the reader to choose two religions studied in class, compare their world outlooks, historical development, and ways of life, and note both their similarities and differences.
XYZ restaurant owner wishes to extend his current operation by.docxwrite5
The XYZ restaurant owner wishes to add an online ordering system to their existing website to allow customers to place takeaway orders via an online chat window. A new computer with a fast internet connection will also be provided at the takeaway counter to receive and process online orders. The project will involve creating a scrolling menu, online chat capability, and order confirmation emails/texts to allow customers to select, pay for, and be notified of their takeaway orders placed online. A project proposal will be developed covering objectives, work breakdown structure, task dependencies, and a network diagram to outline the critical path and timeline to implement the new online ordering system.
Write at least 4 paragraphs in your own words after.docxwrite5
African Americans marched on Washington in 1963 to protest racial inequality and discrimination and demand equal rights and opportunities. There was disagreement between President Kennedy and black leaders over the pace of civil rights reforms. The civil rights movement's goals expanded in the late 1960s to include economic justice and workers' rights, exemplified by the Poor People's Campaign which sought to address issues of poverty across racial lines.
You mention in your post that you will be.docxwrite5
The document asks about expectations for contact with a project manager in the 4 weeks after leaving a facility, what strategies and resources will be left to support the project manager's needs, how involved the project manager has been from the start of the change through transition, and whether stakeholders have buy-in with the project manager.
This document outlines the requirements for a 2-3 page reflection paper on being a minority in a specific situation. Students are asked to describe their experience, reflect on their preconceptions, reactions, and what they learned. They should explain privilege related to their social identity and apply concepts from assigned readings on human rights, social justice, diversity, and being a change agent, citing sources in APA format.
Title Executive Order on Improving the Cybersecurity.docxwrite5
The Executive Order on Improving the Nation's Cybersecurity aims to modernize federal cybersecurity and protect critical infrastructure from cyber attacks. It mandates federal agencies adopt security best practices, tightens standards for software vendors, and requires companies operating critical pipelines to report cyber incidents. The requirement for critical infrastructure operators to immediately report any cyber attacks is the most consequential as it will help the government identify vulnerabilities and threats more quickly.
This document outlines topics to address in a 3-4 page APA formatted paper, including how to develop a coding audit plan by determining the frequency and percentage of charts to audit, how to use OIG work plans and other resources to prepare and update the audit plan, what policies and procedures are needed to monitor for abuse and fraud trends and how they relate to the audit plan, and explaining the interrelationships between providers and payers in audits and monitoring fraud across the healthcare system.
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1. BHS035 Drug Delivery
Answer
Introduction
Drug delivery involves formulations, approaches, manufacturing techniques and storage
systems and technologies for efficiently transporting a pharmaceutical substance or
compound to the target to achieve desired therapeutic effects (Wen et al. 2015). Drug
delivery systems are essentially defined as a device or formulation enabling a therapeutic
drug or substance to selectively reach a desired site of action without reaching organs,
tissues or non-target cells.
Paclitaxel is an effective chemotherapeutic drug developed for acting against broad
disorders of cancers like lung, breast or ovarian cancers (Kampan et al. 2015). Paclitaxel is
encapsulated in non-toxic and biodegradable Nano-delivery systems for protecting it
against degradation. The essay will highlight its reformulation properties and present an
evaluation of the complicated delivery system. It would identify challenges pertaining to the
drug delivery of Paclitaxel and discuss a targeted delivery system for overcoming pertinent
issues.
Discussion
Chosen Drug- Paclitaxel
Paclitaxel is known to be a great antineoplastic drug obtained from natural sources in the
last decade. As a pseudoalkaloid with a taxane ring, it was identified after screening over
35000 plant species for assessing antitumor activity by NCI (National Cancer Institute) in
1958 (Mohanlall and Naicker 2020). However, like other anti-cancer related drugs, issues
are faced in the clinical administration of this drug for the cause of its poor solubility.
Therefore, an adjuvant known as Cremophor EL or polyethoxylated castor oil must be
utilized for its administration. Nanoparticles derived from biodegradable polymers lead to
ideal solutions for the adjuvant issues and realizes the need for implementing a targeted
and controlled drug delivery with lower side effects, reducing severely hypersensitive
reactions and better efficacy.
The most widely utilized formulation of Paclitaxel in clinical settings is the drug’s
2. solubilized form, diluted before its administration intravenously. It contains
polyoxyethylated castor oil (Cremophor EL) in a 1:1 v/v mixture with dehydrated ethanol
(Li et al. 2015). In unopened vials, the drug can remain stable for nearly five years at 4°C in
unopened vials. Cremophor EL is also used in formulations of other hydrophobic agents of
cancer like echinomycin, teniposide, and didemnin B. However, the composition of
Cremophor can cause the release of histamine while inducing hypersensitivity and
hypotension. Thus, paclitaxel formulations need to be infused slowly over several hours for
minimizing the frequency or intensity of side effects. Patients should be pre-medicated with
antihistamines and corticosteroids before the infusion of this drug for preventing
anticipated reactions. Commercially available paclitaxel formulations are diluted about 5-20
times in 5% dextrose solutions and normal saline for administering it intravenously (Zhao
et al. 2019). The resultant formulation is diluted in concentrations of 0.3-1.2 mg/ml of the
drug, which is higher than 0.01 mg/ml paclitaxel’s aqueous solubility, posing pertinent risks
of drug precipitation on diluting it.
The insolubility of Paclitaxel in water causes the formulation to proceed in equal parts of
Cremophor EL and ethanol, helping the drug to be dispersed in an aqueous medium. The
precipitation of the drug has been a major hindrance in its long-term stability while
supporting the utilization of inline filters for infusions. The 2’ position in Paclitaxel’s
structure is ideal for inserting functional groups for creating Paclitaxel pro-drugs, as various
derivatives of 2-acyl Paclitaxel would hydrolyze quickly in the blood (Vagvolgyi et al. 2020).
A C-7 prodrug ester of Paclitaxel can be prepared as the C-7 hydroxyl group arrangement
does not influence cytotoxicity. The presence of a stronger electron releasing substituent,
such as an alkoxy group in the ester’s alpha position, facilitates the quickening of hydrolytic
cleavages. Prodrugs exhibit cytotoxic activities compared to Paclitaxel against cancer in
vitro. Paclitaxel prodrugs formulated utilizing PEG is a promising approach as PEG imparts
efficient aqueous solubility. The pursuit of prodrug designing for industrial efforts focuses
on designing water-soluble derivatives and Paclitaxel’s structural analogues. Paclitaxel is
found in 30 mg (5 ml), 300 mg (50 mL) and 100 mg(16.7 mL) multidose vials (Bhat et al.
2016). Every ml of sterile nonpyrogenic solutions contain 6 mg paclitaxel, 2 mg of
anhydrous citric acid, 527 mg of polyoxyl 35 castor oil, and 49.7% (v/v) dehydrated alcohol.
Cyclodextrins are molecule complexing agents used to increase the stability and solubility of
poorly soluble drugs. Various β? and γ?cyclodextrins such as hydroxypropyl, hydroxyethyl,
and dimethyl enhances the solubility of Paclitaxel by 2*10^3 fold, without altering
cytostatic properties of the drug in-vitro (Raza et al. 2021). The quantity of the solubilized
drug improves with CyD concentration; however, precipitation can be noticed in some
stoichiometries. Therefore, health practitioners should be educated concerning the usage of
accurate non-PVC administration sets and containers for inducing convenience in delivering
Paclitaxel. Studies determine amphoterin B, hydroxyzine, mitoxantrone, chlorpromazine,
and methylprednisolone sodium succinate to be incompatible with infusions of Paclitaxel.
Paclitaxel has the ability of microtubule stabilization and has been associated with
3. platinum-based therapy for the provision of standard care in cancer management. It is a
cytoskeletal drug targeting ‘tubulin’. Cells treated with Paclitaxel usually have deformities in
mitotic spindle assemblies, cell division and chromosome segregation. The drug's
mechanism of action suggests that unlike other drugs that target tubulin like colchicine,
which inhibits the assembly of microtubules, Paclitaxel helps stabilise the microtubule
polymer while protecting it from disassembling (Kampan et al. 2015). Chromosomes
remain unable to achieve a spindle configuration in the metaphase. The progression of
mitosis is blocked, and activation of the mitotic checkpoint for a prolonged duration triggers
reversion to the G0 phase of the cell cycle without undergoing cell division or apoptosis.
Paclitaxel’s ability to hinder spindle function is attributed to suppressing the dynamics of
microtubules. However, it occurs at concentrations lower than what is required to block
mitosis. Paclitaxel suppresses the detachment of microtubules from centrosomes at high
therapeutic concentrations, a process activated in mitosis. Paclitaxel effectively binds to
‘beta-tubulin’ sub-unis in microtubules. Unlike vinca alkaloids, which cause microtubule
depolymerization, Paclitaxel acts during the mitotic stage of cellular division. Paclitaxel also
activates multiple pathways of signal transduction, which is linked with proapoptotic
signalling (Lee et al. 2015). The associated pathways with Paclitaxel are TLR-4 dependent
pathway, the c-Jun N-terminal kinase pathway, P38 mitogen-activated protein kinase,
nuclear factor-kappa, and transcription factor activator pathway. Induction of pro-
inflammatory proteins and cytokines would lead to immune-modulatory effects at low-
dosage concentrations and higher doses, inducing cell death. At concentrations of less than
9 nM, Paclitaxel activates Raf-1, responsible for controlling apoptosis (Ozfiliz et al. 2015). At
more than 9 nM, there is an absence of the involvement of Raf-1 kinase, but apoptosis is
induced for the impact of p53 and p21. With similar concentrations but over 24-hour
exposure, a mitotic arrest can be caused irreversibly. Weekly paclitaxel administration
exhibits inhibitory angiogenic activity.
Extracting Paclitaxel from its plant origin, Taxus brevifolia kills many plants for yielding a
few grams of the drug (Zhu and Chen 2019). Consequently, a practical synthetic procedure
of paclitaxel production requires the development of challenges due to the structural
complexities. The current production of Paclitaxel industrially occurs through a technology
of paclitaxel fermentation, where Paclitaxel can be extracted efficiently from cultured cell
lines of Taxus, which can be purified using chromatography. Paclitaxel has a diterpenoid
structure around complex, bulky, and fused taxane rings while containing multiple
hydrophobic substituents, making it a greatly lipophilic compound with aqueous solubility
lesser than 0.01 mg/ml. In addition, the compound does not contain functional groups that
are potentially ionizable, leading to its increase in solubility with altering pH. Among
various non-aqueous solvents, the solubility has been traced to be nearly 46 mM for
ethanol, nearly 20 mM in acetonitrile or methylene chloride, and about 14 mM for
isopropanol. It also shows solubility in tertiary-butanol, methanol and dimethyl sulfoxide.
To decrease toxic effects linked to conventional formulations of Paclitaxel discussed before
while minimizing precipitation risks of Paclitaxel on dilution, a nanoparticle formulation for
4. Paclitaxel has been introduced called Abraxane (Zhao et al. 2015). Particle formation
technology involves a proprietary process binding unmodified albumin to the molecule of
Paclitaxel for producing conjugate masses less than 130 nm size. On infusion, the
nanoparticles dissociate rapidly to yield an albumin-bound drug aggregate. Paclitaxel-
albumin molecules bind to albumin receptors (gp60) on endothelial cells. It helps in the
transportation of Paclitaxel via caveolae formation into extravascular spaces.
An alternate pathway for transport has been considered for binding the nanoparticles with
SPARC or “secreted acidic protein rich in cysteine” (Noorani et al. 2015). However, Sparc
remains overexpressed in various solid tumours, including prostate and bladder cancers, so
the nab-paclitaxel causes a 33% rise in intra-tumoral concentrations and a 50% high
paclitaxel dose delivered in comparison to Paclitaxel infusion, occurring conventionally.
Moreover, as the nab-paclitaxel is solvent-free, there is a shorter infusion time than
Paclitaxel mixed with Cremophor EL.
Among alternative systems of experimental delivery of Paclitaxel, the nanoparticles from
various bio-adhesive materials and biodegradable polymers have been promisingly
considered. Nanotechnology helps improve the bioavailability of poorly soluble drugs while
enhancing the overall system of drug delivery. Nanoparticles can permeate through tissues
without adding to their potential of drug targeting. Therefore, the drug delivery should
occur efficiently to the targeted tissue without clogging the capillaries to protect the drug’s
stability and bioactivity. On incorporating Paclitaxel into nanoparticles, drug action has had
a demonstrable enhancement for the notable changes in pharmacokinetics and tissue
distribution. Nanoparticles can also evade quick clearance through the reticuloendothelial
system and accumulate preferentially in solid tumours by escaping prevalent angiogenic
vasculatures that permeate through the neoplasm (Kianfar 2021). The delivery of drugs in
nanoparticle carriers lead to an extension of drug retention in tumours, causes prolonged
survival of test subjects, and diminution in the growth of tumours.
Furthermore, the phenotype of multidrug resistance mediated by p-glycoproteins of tumour
cells can be overcome by utilizing nanoparticle delivery of the drug. It is significant as the
acquired resistance for Paclitaxel can be reported. Additional advantages of nanoparticles
are levied due to their enhanced stability mode, for biological fluids or during storage.
Preparation of Paclitaxel nanoparticles utilizing the method of interfacial deposition can be
observed. An organic PLGA solution in acetone with Paclitaxel can be added to an aqueous
poloxamer 188 solutions. It is observed at room temperature through constant stirring
using magnetic fields, followed by harvesting and washing the nanoparticles using
ultracentrifugation. In vitro studies examine the conduction of measuring residual paclitaxel
amount at particular time points after having the PLGA-nanoparticles consisting of
Paclitaxel diluted in PBS solution and incubated in horizontal shakers at 37°C (Madani et al.
2018). The particles exhibit biphasic patterns for releasing Paclitaxel, along with a fast
release on the first day and constant slower release later.
5. Liposomes are lipoid vesicles offering flexible platforms for encapsulating hydrophilic and
lipophilic drugs. Lipophilic drugs attain a lipid bilayer while hydrophilic drugs remain
located in the vesicle cavity. When drugs are encapsulated in liposomes, a change in
pharmacodynamics and pharmacokinetic properties results in a reduction of toxicity and an
increase in drug potency. The preparation and characteristic sterile stabilization of
Paclitaxel- liposomes are compared to conventional liposomes loaded with Paclitaxel due to
its circulation in blood for extended periods. PEGylated liposomes are prepared using
Paclitaxel with cholesterol and phospholipids in the molar ratio of 1:30 (Mol drug: Mol
lipid). Incorporating more than 20% cholesterol decreases formulations' physical stability
and incorporation efficiency (Lee 2020). The spleen and liver distribution of PEGylated
liposomes consisting of Paclitaxel have been evaluated after Paclitaxel extraction from the
tissues using “t-butyl methyl ether”. These formulations have been assessed to be well-
tolerated in mice when administered via intraperitoneal and intravenous bolus doses. The
maximum dose that can be tolerated has been deduced to be within 200 mg/kg in the case
of liposomal Paclitaxel and 30 mg/kg by Intravenous administration, or50 mg/kg for free
Paclitaxel via Intra-peritonial routes.
Conclusion
The maintenance of a proper procedure to administer drugs or pharmaceutical components
correctly for humans and animals is of paramount importance to derive positive outcomes.
The product needs to be stable and adequate delivery maintenance under different
physiological variables. After a broad field of research on novel conventional approaches for
delivering Paclitaxel, the acknowledgement of controlled, steady and effective therapeutic
delivery has been examined. Cremophor EL can enhance the solubility and dispersion of
Paclitaxel in an aqueous medium. Nanoparticles have been considered for aiding Paclitaxel
delivery approaches by utilizing a formulated compound called Abraxane. Environmental-
friendly processes can produce naturally derived pharmaceutical ingredients from plant
cells. Paclitaxel administration as 1-hour infusions through weekly and 3-week treatment
regimens can actively treat various tumours and carcinomas, inducing unknown primary
sites.
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