In recent years, robustness and surface engineering of dosage form made improvement in pharmacokinetics with decrease in dose of drug. Specificity with adherence of ligands has now become the reality as surface modifi cation can easily deceive phagocytic system. Lipid molecules ensures the
release of drug at lymphatic system, entrapment of polymeric nanoparticles in lipoidal core led to the
avoidance of disadvantage of low entrapment effi ciency if use of hydrophobic drug with hydrophobic polymer becomes essential. Various studies have been published and the best formulations with optimal In vitro and In vivo results are highlighted in this paper. In this review most advanced researches and accepted patents were discussed so to act as a medium for getting everything regarding lipid polymer hybrid particles under one umbrella.
Biodegradable polymers based transdermal drug delivery systemDeepanjan Datta
Friends..me and my best buddy miss.pragya paramita pal prepared this presentation during the last semester of our graduation.I am just uploading this so that this can help you to prepare better presentations based on such topics.Thanks to my guide and my friend miss.pragya.Enjoy friends & best of luck..
Polymer-drug conjugates are a novel class of nanocarriers for drug delivery, which can protect the drug from premature degradation, prevent the drug from premature interaction with the biological environment and enhance the absorption of the drugs into tissues (by enhanced permeability and retention effect or active targeting).
Polymer-drug conjugates are often considered as new chemical entities (NCEs) owing to a distinct pharmacokinetic profile from that of the parent drug.
Conjugation of a drug with a polymer forms so-called ‘Polymeric Prodrug’.
Biodegradable polymers based transdermal drug delivery systemDeepanjan Datta
Friends..me and my best buddy miss.pragya paramita pal prepared this presentation during the last semester of our graduation.I am just uploading this so that this can help you to prepare better presentations based on such topics.Thanks to my guide and my friend miss.pragya.Enjoy friends & best of luck..
Polymer-drug conjugates are a novel class of nanocarriers for drug delivery, which can protect the drug from premature degradation, prevent the drug from premature interaction with the biological environment and enhance the absorption of the drugs into tissues (by enhanced permeability and retention effect or active targeting).
Polymer-drug conjugates are often considered as new chemical entities (NCEs) owing to a distinct pharmacokinetic profile from that of the parent drug.
Conjugation of a drug with a polymer forms so-called ‘Polymeric Prodrug’.
Mucoadhesive drug delivery system has gained interest among pharmaceutical scientists as a means of promoting dosage form residence time as well as improving intimacy of contact with various absorptive membranes of the bio- logical system
“Microparticles are defined as particulate dispersions or solid particles with a size in the range of 1-1000 μm.”
The drug is dissolved, entrapped, encapsulated or attached to a microparticle matrix.
Microspheres are spherical & free flowing particles ranging in average particle size from 1 to 50 microns which consist of proteins or synthetic polymers. Some of the problems of overcome by producing control drug delivery system which enhances the therapeutic efficacy of a given drug. One such approach is using microspheres as carriers for drugs. The target site drug deliver with Specificity & maintain the concentration at site of interest without untoward effects. It will find the central place in novel drug delivery. Drugs can be targeted to specific sites in the body using microspheres. Degree of targeting can be achieved by localization of the drug to a specific area in body (for example in lungs), to a particular group of cells and even to the intracellular structures. The rate of drug release from the microspheres dictates their therapeutic action.
Novel Drug Delivery System An OverviewYogeshIJTSRD
In present scenario evolution of an existing drug molecule from a old form to a novel delivery system can significantly improve its performance in terms of patient compliance, safety and efficacy. In the form of a control drug delivery system an existing drug molecule can get a new life. An appropriately designed Novel Drug Delivery System can be a major advance for solving the problems related towards the release of the drug at specific site with specific rate. The porpuse for delivering drugs to patients efficiently and with fewer side effects has prompted pharmaceutical companies to engage in the development of new drug delivery system. This article covers the basic information regarding Novel Drug Delivery Systems and also advantages, factor etc. Chiranjit Barman | Dr. Gaurav Kumar Sharma | Dr. Kausal Kishore Chandrul "Novel Drug Delivery System: An Overview" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd45068.pdf Paper URL: https://www.ijtsrd.com/pharmacy/novel-drug-delivery-sys/45068/novel-drug-delivery-system-an-overview/chiranjit-barman
Mucoadhesive drug delivery system has gained interest among pharmaceutical scientists as a means of promoting dosage form residence time as well as improving intimacy of contact with various absorptive membranes of the bio- logical system
“Microparticles are defined as particulate dispersions or solid particles with a size in the range of 1-1000 μm.”
The drug is dissolved, entrapped, encapsulated or attached to a microparticle matrix.
Microspheres are spherical & free flowing particles ranging in average particle size from 1 to 50 microns which consist of proteins or synthetic polymers. Some of the problems of overcome by producing control drug delivery system which enhances the therapeutic efficacy of a given drug. One such approach is using microspheres as carriers for drugs. The target site drug deliver with Specificity & maintain the concentration at site of interest without untoward effects. It will find the central place in novel drug delivery. Drugs can be targeted to specific sites in the body using microspheres. Degree of targeting can be achieved by localization of the drug to a specific area in body (for example in lungs), to a particular group of cells and even to the intracellular structures. The rate of drug release from the microspheres dictates their therapeutic action.
Novel Drug Delivery System An OverviewYogeshIJTSRD
In present scenario evolution of an existing drug molecule from a old form to a novel delivery system can significantly improve its performance in terms of patient compliance, safety and efficacy. In the form of a control drug delivery system an existing drug molecule can get a new life. An appropriately designed Novel Drug Delivery System can be a major advance for solving the problems related towards the release of the drug at specific site with specific rate. The porpuse for delivering drugs to patients efficiently and with fewer side effects has prompted pharmaceutical companies to engage in the development of new drug delivery system. This article covers the basic information regarding Novel Drug Delivery Systems and also advantages, factor etc. Chiranjit Barman | Dr. Gaurav Kumar Sharma | Dr. Kausal Kishore Chandrul "Novel Drug Delivery System: An Overview" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd45068.pdf Paper URL: https://www.ijtsrd.com/pharmacy/novel-drug-delivery-sys/45068/novel-drug-delivery-system-an-overview/chiranjit-barman
Polymer therapeutics: an smart drug delivary systemAlok kumar Soni
The development of polymer therapeutics has emerged as an exciting field of research for improving the therapeutic potential of low-molecular-weight drugs and proteins. this presentation depicted overview of nanomedicine in healthcare industry
Piroxicam Nanostructured Lipid Carrier Drug Delivery SystemYogeshIJTSRD
Objective Nanostructured lipid carrier NLC based topical gel of Piroxicam PXM was formulated with the aim of controlled release action and to reduce systemic side effect for the treatment of an arthritic condition. Methods NLCs developed using high pressure homogenization method and optimized using a 32 factorial design with response surface methodology using design expert software. NLCs were characterized for particle size, zeta potential analysis, drug entrapment efficiency, and in vitro drug release studies to select the optimized formulation. The NLCs were suitably gelled and evaluated with respect to homogeneity, pH, viscosity, gel strength, spread ability, rheological characteristics, drug content, in vitro diffusion, and stability study. Safety of the NLC based gel was assessed using primary skin irritation studies, and efficacy was confirmed using carrageen an induced rat paw edema model. Results NLCs formulation comprising 2 of lipid 60 40 and surfactant 1.50 was confirmed as an optimized batch having a particle size 138.2±3.60 nm with polydispersibility index value 0.344±0.034. The zeta potential value indicates good physical stability. Based on the results from the in vitro release study it was shown that the formed gels had the ability to extend release of PXM for 24 h and showing percentage drug release of 90.92 ±1.96 at the end of 24 h. Skin irritation studies revealed that the optimized gel formulation shows no erythema, edema, or ulceration. Conclusion The overall results of the present study clearly indicated promising potentials of NLC based gel for delivering PXM topically over the conventional gel. Dr. G. Jagadish | Dr. Rita Mourya | Dr. Amith Nayak "Piroxicam Nanostructured Lipid Carrier Drug Delivery System" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-3 , April 2021, URL: https://www.ijtsrd.com/papers/ijtsrd39912.pdf Paper URL: https://www.ijtsrd.com/pharmacy/pharmaceutics/39912/piroxicam-nanostructured-lipid-carrier-drug-delivery-system/dr-g-jagadish
Dissolution Enhancement of BCS Class 4 Dssrugs Using Quality by Design Approa...inventionjournals
Solid dispersion is one of the vastly accepted and practically economical processes in bioavailability enhancement study. The present investigation deals mostly with increase in solubility and dissolution rate of BCS class 4 drugs for enhancement of oral bioavailability. For the same solid dispersion were prepared and analyzed for appropriate concentration of drug polymer ratio by phase solubility analysis. The solvent evaporation study widely accepted due to its efficient solid dispersion in lesser efforts. The study designs were prepared with specific concentration of drug and polymer ratio with the help of high throughput model i.e. Central Composite Design (by Design Expert trial copy) by specific design of experiment with full factorial design (DOE). The fixed variables were concentration of polymers and dependant variables were dissolution and permeability across bio-membrane in in-vitro model. The prepared dispersion investigated for dissolution and permeability improvement using USP Type II apparatus and modified everted gut sac model which leads to improvement of quality of whole formulation with Quality by design efficiently.
Ten Reliable Sources to Learn About Journal of Nano Medicine and Nanotechnologyscience journals
The nano medicine Journal enjoys reputation and popularity among the medical practitioners, as a novice technology in the biomedical research that offers innovative therapeutic practices. Nanotechnology as a medical application offers plethora of opportunities for the practitioners to explore innovative ways of drug delivery systems, therapies and In vivo imaging techniques.
PROTAC Delivery System Recent Research Advances.pdfDoriaFang
The combination of PROTAC and multifunctional delivery systems will open up new research directions in the field of TPD. Here we will introduce the combination of PROTAC and multifunctional delivery systems.
Recent Advancement and Patents of the Lipid Polymer Hybrid Nanoparticlespeertechzpublication
In recent years, robustness and surface engineering of dosage form made improvement in
pharmacokinetics with decrease in dose of drug. Specifi city with adherence of ligands has now become
the reality as surface modifi cation can easily deceive phagocytic system. Lipid molecules ensures the
release of drug at lymphatic system, entrapment of polymeric nanoparticles in lipoidal core led to the
avoidance of disadvantage of low entrapment effi ciency if use of hydrophobic drug with hydrophobic
polymer becomes essential. Various studies have been published and the best formulations with optimal
In vitro and In vivo results are highlighted in this paper. In this review most advanced researches and
accepted patents were discussed so to act as a medium for getting everything regarding lipid polymer
hybrid particles under one umbrella.
Vibrational Characterization and Antioxidant Activity of Newly Synthesized Ga...peertechzpublication
The gallium(III) complex of orotic acid (HOA) was synthesized and its structure was determined
by means of analytical and spectral analyses. Detailed vibrational analysis of HOA, sodium salt of HOA
(NaOA) and Ga(III)-OA systems based on both the calculated and experimental spectra confi rmed the
suggested metal-ligand binding mode. Signifi cant differences in the IR and Raman spectra of the complex
were observed as compared to the spectra of the ligand and confi rmed the suggested metal-ligand
binding mode.
Synthesis and Antimicrobial Evaluation of Some Nitro-Mannich Bases Derived fr...peertechzpublication
The present work focused on exploring the reactivity of β-nitrostyrene towards Mannich reaction
with different approaches. The synthesized nitro-Mannich bases were tested as antimicrobial agents
that showed high activity against both gram positive and gram negative bacteria.
Recent Structure Activity Relationship Studies of 1,4-Benzodiazepinespeertechzpublication
Structure activity relationship studies of 1,4-benzodiazepines have been discussed especially
with their effects as antianxiety and anticonvulsants. The currently available benzodiazepines are
associated with various side effects. Nowadays the purpose of these studies is to minimize side effects
with these drugs. A very little alteration is possible on the benzene ring while the modification can be
done on the diazepine ring. It can adopt the different conformations and in some cases some aromatic
and heterocyclic rings have been fused with this part in order to see the effect of these conformation
blockers on the pharmacological activity. The structure activity studies are also linked to molecular
modeling studies. This is important in adding some information for the interaction of these drugs with
the receptors and how this interaction can be improved.
Microwave Irradated Synthesis, Characterization and Evaluation for their Antibacterial and Larvicidal Activities of some Novel Chalcone and Isoxazole Substituted 9-Anilino Acridines
drug delivery and formulation sciences in the most intelligent
way. This should be attained to fulfi l the ultimate goal for all
scientists to leave their experimental results all over the years
as footsteps for followers to walk on.
Mycobacterium Tuberculosis cause severe disease of lungs known as Tuberculosis. It is a major cause
of morbidity and mortality even in the emerging countries also. However, to prepare an antibiotics drug against Mycobacterium tuberculosis is a major challenge
Mini tablets are solid dosage forms with a diameter ≤ 3 mm and separated into subunits of conventional
tablets. Production methods are similar to standard tablets, but the only difference is the use of multiple
punches. They have advantageous for use in patients suffering from swallowing difficulty and receiving multiple drug treatment.
Drug-Drug interactions (DDI) is a serious clinical issue. An important mechanism underlying of DDI, is
induction or inhibition of drug metabolizing enzymes (DMEs) and transporters that mediate metabolism, cellular uptake and efflux of xenobiotics. DDI cannot be avoided in many cases, as they belong to routine medical practice.
Few species are standardized and have been used as test organisms around the world in
ecotoxicological assays. In the case of sediment assessment, there are only two amphipod species
(Tiburonella viscana and Grandidierella bonnieroides) standardized protocols for toxicity test in South
Atlantic region
Gigantic submarine landslides are among the most energetic events on the Earth surface. During the
Late Pleistocene the Mediterranean Sea was the scenario of a 9 number of such events, some of whose
geological fi ngerprints are the 500 km3 mass transport deposit SL2 at the Nile delta fan (dated at ca. 110
ka BP) and the Herodotus Basing Megaturbidite (HBM, a 400 km3 deposit dated at ca. 27.1 ka BP).
Natural frequency of structure mainly depends on mass and stiffness. Stiffness is bound to change
after structural damage. Hence, natural frequency starts to decline.
In this study, the green-lipped mussels Perna viridis were collected from a high activity sampling at
Senibong in the Straits of Johore and two relatively clean sites with fi sh aquacultural activity at Bagan
Tiang (Perak) and Sg. Semerak (Kelantan). The mussels were dissected by gender into byssus, crystalline
style, foot, gill, gonad, mantle and muscle.
The current study examines the generation and propagation of a Third order solitary water wave along
the channel. Surface displacement and wave profi le prediction challenges are interesting subjects in the
fi eld of marine engineering and many researchers have tried to investigate these parameters. To study the
wave propagation problem, here, fi rstly the meshless Incompressible Smoothed Particle Hydrodynamics
(ISPH) numerical method is described. Secondly,
The growth of data and its effi cient handling is becoming more popular trend in recent years bringing
new challenges to explore new avenues. Data analytics can be done more effi ciently with the availability of
distributed architecture of “Not Only SQL” NoSQL databases.
In modern mechanical engineering and steelwork the use of cold-rolled steel sections is a
standard method. These sections should be mechanically stable on the one hand and cost efficient on
the other hand. To decide what profile suits for a certain case is a constrained optimization problem which is in general non convex, i.e. several local optima exist.
Few species are standardized and have been used as test organisms around the world in
ecotoxicological assays. In the case of sediment assessment, there are only two amphipod species
(Tiburonella viscana and Grandidierella bonnieroides) standardized protocols for toxicity test in South
Atlantic region.
Gigantic submarine landslides are among the most energetic events on the Earth surface. During the
Late Pleistocene the Mediterranean Sea was the scenario of a 9 number of such events, some of whose
geological fi ngerprints are the 500 km3 mass transport deposit SL2 at the Nile delta fan (dated at ca. 110
ka BP) and the Herodotus Basing Megaturbidite (HBM, a 400 km3 deposit dated at ca. 27.1 ka BP). This
paper presents an exploratory study on the tsunamigenic potential of these slides by using a numerical
model based on the 2D depth-averaged non-linear barotropic shallow water equations.
Introduction: The aim of this study is to evaluate, within the scope of an experimental design, to
what extent the assessment of two different settings of prepared cavities, based on video sequences,
containing digital analysis tools of the prepCheck software, as well as to what extent they deviate from one another and are reliable. Materials and Methods: For
Predicting the amount of electricity produced in a power plant is very important for today’s economy.
Oven Power (MW), Boiler Input Gas Temperature, Superheated Steam Amount, ID-Fan Speed, Feeding
Water Tank data affect the electricity production.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Triangles of Neck and Clinical Correlation by Dr. RIG.pptx
Open Journal of Chemistry
1. vv
Open Journal of Chemistry
CC By
025
Citation: Kasera NK, Sharma PK, Gupta R (2015) Recent Advancement and Patents of the Lipid Polymer Hybrid Nanoparticles. Peertechz J Med Chem Res 1(1):
025-029. DOI: http://dx.doi.org/10.17352/ojc.000005
Chemistry Group
http://dx.doi.org/10.17352/ojc.000005DOI
Abstract
In recent years, robustness and surface engineering of dosage form made improvement in
pharmacokinetics with decrease in dose of drug. Specificity with adherence of ligands has now become
the reality as surface modification can easily deceive phagocytic system. Lipid molecules ensures the
release of drug at lymphatic system, entrapment of polymeric nanoparticles in lipoidal core led to the
avoidance of disadvantage of low entrapment efficiency if use of hydrophobic drug with hydrophobic
polymer becomes essential. Various studies have been published and the best formulations with optimal
In vitro and In vivo results are highlighted in this paper. In this review most advanced researches and
accepted patents were discussed so to act as a medium for getting everything regarding lipid polymer
hybrid particles under one umbrella.
Research Article
Recent Advancement and Patents
of the Lipid Polymer Hybrid
Nanoparticles
Naman Krishna Kasera*, Pramod
Kumar Sharma and Rahul Gupta
Department of Pharmacy, School of Medical and
Allied Sciences, Galgotias University, Greater Noida,
UP, India
Dates: Received: 15 December, 2016; Accepted: 29
December, 2016; Published: 31 December, 2015
*Corresponding author: Naman Krishna Kasera,
Department of Pharmacy, School of Medical and
Allied Sciences, Galgotias University, Plot No. 17A,
Yamuna Expressway, Greater Noida, UP, India, Tel:
+919451327322; E-mail:
Keywords: Lipid polymer hybrid nanoparticles; Core
shell structure; Tumor targeting; Liposomes; Supra-
molecular
https://www.peertechz.com
Abbreviations
EPR: Enhanced Permeability and Retention; MPS:
Mononuclear Phagocyte System; PLGA: Poly D,L-Lactic-Co-
Glycolic Acid; PEG: Polyethylene Glycol; Nps: Nanoparticles;
RES: Reticuloendothelial System; DOTAP: 1,2-Di-(9Z-
Octadecenoyl)3-Trimethyl Ammonium Propane; DMAB:
Dimethyldidoceylammonium Bromide; DPPC: 1,2-Dipalmitoyl-
Sn-Glycero-3-Phosphocholine; DSPE: 1,2-Distearoyl-Sn-
Glycero-3-Phosphoethanolamine-N-[Methoxy(Polyethylene
Glycol)-2000; HSPC: Hydrogenated Soy Phosphatidylcholine;
DNA: Deoxyribo Nucleic Acid; RNA: Ribonucleic Acid
Introduction
In the past century, there has been much research analysis
towards achieving a better concept of cancer causing agent,
diagnosis treatment and cure [1]. The main focus relies towards
understanding the peculiar microenvironment of tumor which
acts as one of the barrier of drug targeting often results into
systemic toxicity as well as various undesirable side effects
[2]. The unusual tumor vasculature and its unregulated growth
comprises of heterogeneous blood flow and vascular resistance
often leads to poor therapeutic response of drug administered
with multiple drug resistance mechanism shown by the tumor
cells [3,4]. During such conditions tumor vasculature can also
be characterized by distorted vascular permeability, elevated
interstitial pressure, extracellular acidosis and hypoxia [5].
From long time back all such factors were studied by pool of
eminent scientists for tumor targeting of chemotherapeutic
agents. One such targeting mechanism based upon tumor
vasculature was called as enhanced permeability and retention
(EPR) effect in which tumor vasculature shows enhanced
permeability allowing large molecules and lipids to easily enter
the extravascular space in tumors and finally retains there
due to poor development in lymphatic drainage [6], [7,8].
The circulation of colloidal carriers in systemic circulation so
that to reach its target site is also one of the deciding factor
affecting tumor targeting as mononuclear phagocyte system
(MPS) rapidly use to uptake colloidal particles via process
of opsonization [9,10]. Surface engineering of colloidal
carriers for increasing the circulation time of carriers was
the development made to deceive reticuloendothelial system
to avoid opsonization [11]. Thus, it can be inferred that the
development of lipoidal colloidal carriers with stealth nature
can be used as drug delivery approach for achieving better
tumor targeting. This is done through PEGylation of the
surface ensuring the “stealth” property. While various natural
polymer such as dextans, pullalans, gangliosides have also
been used for such stealth property [12,13]. In one research
work, salidroside entrapped lipid polymer nanoparticles were
formulated using PLGA-PEG-PLGA sequences of the polymer
and lecithin and cholesterol as lipid and the evaluation result
obtained for the formulated nanoparticles showed (65%)
entrapment efficiency, 150nm size, and surface was negatively
charged (-23mV). It could efficiently release salidroside from
the nanoparticles and the drug act against the tumour cells. It
2. Kasera et al. (2016)
026
Citation: Kasera NK, Sharma PK, Gupta R (2016) Recent Advancement and Patents of the Lipid Polymer Hybrid Nanoparticles. Peertechz J Med Chem Res 2(1):
009-029. DOI: http://dx.doi.org/10.17352/ojc.000005
selectively showed antitumour activity against PANC-1 and 4T1
cancer cell lines [14]. So, the main focus of this article was to
illuminate the effectiveness of newly developed lipid polymer
hybrid nanoparticles for its use in tumor targeting through
recent research publications as well as various patents.
The concept of prod rug for its unrecognization for
opsonization as well as cleavage mechanism at target site
is the only approach which can be used for tumor targeting
of chemotherapeutic agents [2]. The development of such
delivery system requires the conjugation of chemotherapeutic
agent with tumor recognition moiety to which suitable linkers
are attached and having an outer layer of stealth polymer
[15]. Hybrid lipid-polymer nanoparticles acting as one of the
conjugate system can be used for tumor targeting [16]. The
patented technique was published in 2008. The invention was
related to the development of nanoparticulate colloidal delivery
vehicle comprising a hydrophobic biodegradable polymer in
blend with a hydrophobic lipid component which is either
PEGylated phospholipid or simple phospholipid with attached
targeting / recognizing compounds [17]. The development
of lipid polymer hybrid nanoparticles was mainly related to
mitigate the limitations associated with liposomes as well
as nanoparticles [18]. Polymeric NPs which are suitable for
systemic administration may be produced by self-assembly
of biodegradable copolymers consisting of two or more
polymer blocks with different hydrophobicities. NPs were
mixed with liposomes to form lipid-polymer complexes such
as lipoparticles where the lipid bilayer fuses on the surface of
polymeric NPs. In one research, the authors had relied upon the
use of two preparation techniques, one being, two-step process
in which polymer core and lipid shell are produced individually
and then mixed whereas the second method is a single step
process by nanoprecipitation and self-assembly process [19].
In a study, it was found that macromolecules with
molecular weight ranging from 15000 to 70000 g/mol could
easily segregate at the solid tumour site with an ease. Although,
the size of the nanoparticles is an important property for the
accumulation at tumour site. This was further elaborated by
comparing the smaller and larger sized particles wherein the
smaller molecules accumulated at the target site much faster
but larger molecules remain accumulated for a much longer
period of time. Hence, size is an important parameter to be
taken into consideration [20]. The size of the nanoparticles
reported to be less than 200nm can efficiently had a longer
circulation time because of low uptake by Reticuloendothelial
system (RES). While the nanoparticles having size of 400nm
were capable to reach the tumour extravasculature. The
nanoparticles of 500nm were defined to be the maximum size
to move across the cell membrane [21].
Several studies have been focusing on the lipid uptake
and its metabolism. One study discussed about the methods
eg. Adsorption, flip flop, acidification of micelles, uptake
accompanied through hepatocytes etc [22].
In one research work, lipid polymer hybrid nanoparticles
were produced by a pattern tunnable microvortex ensuring
increase in production with proper efficiency in size. Solution of
PLGA dissolved in acetonitrile from central outlet and lecithin
and DSPE-PEG (lipid PEG) in 4% ethanol aqueous solution in
outer outlet were passed through microfluidic channels and
mixed rapidly. It was observed that by differing the flow rates,
the size of the nanoparticles could be controlled and high
productivity could be maintained [23]. In another work, author
had demonstrated the in-situ polymerization of soyabean oil.
In this, soyabean oil of different concentration was interacted
with mineral medium comprising 1%w/vNH4
NO3
, 2.55%w/v
NaH2
PO4
, 0.5%w/v MgSO4
.7H2
O, 0.1%w/v CaCl2
.H2O, 0.02
%w/v MnSO4
.H2O, 1%w/v Peptone and 0.5%w/v Glucose was
incubated with agitation (200rpm) at 37o
C for 240 hours. The
self-assembled multilayered nanoparticles was characterized
and was suitable for both hydrophilic and hydrophobic drugs
becauseuseofamineralmediumeasedentrapmentofhydrophilic
and soyabean oil being the entrapment site for hydrophobic
drugs. The size of the particles obtained was approximately
2 cm in diameter [24]. One such effort used double emulsion
technique for the formulation of solid lipid nanoparticles
(SLNs). It made use of Methocel as the polymer. These hybrid
nanoparticles were used for the oral drug delivery of insulin
because methocel lipid nanoparticles prevent the degradation
of insulin which was done by chymotrypsin, an intestinal
enzyme, at the gastrointestinal pH. These demonstrated with
enhanced or doubled entrapment efficiency of the insulin.
The methocel hybrid nanocarrier ensured overcome of other
drawbacks of the oral drug delivery such as cytotoxicity [25].
The other work was to establish influence of the cationic
lipid on the properties of Lipid polymer hybrid nanoparticles.
The work includes the preparation of nanoparticles using
PLGA (poly D,L-lactic-co-glycolic acid) core and 1,2-di-(9Z-
octadecenoyl)3-trimethyl ammonium propane (DOTAP) as
cationic lipid by emulsion solvent evaporation method using
different concentration of lipid. It had better plasmid DNA
binding capacity [26]. Another work was ensured bypassing
of multidrug resistance in cancer cells. The nanoparticles was
prepared using dimethyldidoceylammonium bromide (DMAB),
modified poly lactic-co-glycolic acid (PLGA) surrounded
by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)
shell and Doxorubicin as a P-glycoprotein substrate. The
nanoparticles have increased accumulation in drug resistant
cells with its size approximately 200nm and loading content
was 0.71%+- 0.06% [27]. In other research, gelatin (Type
a , cationic below its isoelectric point (7.0-9.0) as polymer ,
lecithin as lipid was cored with Amphotericin B by two step
desolvation method for the improved oral bioavailability.
The particle was of size range 253+- 8nm and 50.61+- 2.20%
entrapment efficiency and 0.274 +- 0.008 polydispersity
index was obtained [28]. The research was done for the dual
targeting of the nanoparticles. It was prepared to target solid
gastric tumour having Her2 and CD44 wit loaded SN38. The
nanoparticles was prepared using biodegradable polymer PLGA
and lipid shell of AHNP peptide and n-hexadecylamine (HAD)
to the carboxyl group of Hyaluronic acid (HA). The particle was
of size range 353.6- 532.9 nm and specifically blocking CD44
and Her2 [29].
In a work by researchers, the core shell lipid polymer hybrid
nanoparticles was prepared and loaded with Erlotinib. It was
3. Kasera et al. (2016)
027
Citation: Kasera NK, Sharma PK, Gupta R (2016) Recent Advancement and Patents of the Lipid Polymer Hybrid Nanoparticles. Peertechz J Med Chem Res 2(1):
009-029. DOI: http://dx.doi.org/10.17352/ojc.000005
preparedbysinglestepsonicationmethodusingpolycaprolactone
(PCL) as polymeric core and phospholipid shell composed
of 1,2-distearoyl-sn- glycero-3-phosphoethanolamine-
N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG2000)
and hydrogenated soy phosphatidylcholine (HSPC). It was
characterized with mean size of 170nm and 66% entrapment
efficiency [30]. Further, the work moved towards the use of
natural polymer, Chitosan was used for oral drug delivery of
insulin using hybrid nanoparticles. The lipid nanoparticles
(LNPs) were of size 265.3+-34 nm to 387.4+- 35.6 nm and
85% entrapment efficiency [31]. In a recent contribution
towards the advancement of hybrid nanoparticles, the core
shell nanoparticles were achieved for the delivery of small
interfering RNA. The hybrid nanoparticles was prepared by
using PLGA as inner polymer layer, PEG as outer layer, while
in between these two layer a lecithin layer was present. The
hollow core entrapped and reported targeted gene delivery of
the small interfering RNA [32].
Patents associated with lipid polymer hybrid nanopar-
ticles
1. Hybrid lipid polymer nanoparticulate delivery
composition: The innovators provides with a
biocompatible, stable polymer lipid hybrid nanoparticle.
The formulation had no such characteristic of phase
separation, drug leaking and precipitation. It was also
observed that combination of biodegradable polymer
with solid lipids have showed good drug loading,
stability and possibility of regulating release patterns
and degradation parameters. Hybrid polymer-lipid
nanoparticles (HPLNP) comprised a biodegradable
polymer, e.g., polycaprolactone (PCL), polylactic-
polyglycolic copolymer (PLGA) and a solid lipid, e.g.,
tripalmitin, glycerin stearate, tristearin, cholesterol,
tocopherol palmitate, tocopheryl succinate, stearyl
stearate, tribehenin, cetostearyl alcohol, benzoyl
behenate, stearic acid, camauba or cande lilla wax,
cocoa butter, SuppocireTM CM/DM, WecobeeTM M
and other lipids, having a melting point past 20° C i.e.,
solid at room temperature. In one such formulation,
PLGA , as polymer, Tristerin , as lipid, ethylacetate ,
as solvent was used and obtained nanoparticles of 185
nm with 95% yield while in other cases they used PCL
, Cholesterol , and ethylacetate and resulted into 100%
yield with size of 101nm [33].
2. Adjuvant incorporation of immunotherapeutics:
This invention ensures composition and system for
delivery of nanoparticle towards the stimulation of
cells of immune system as the nanoparticles was
used to entrap various immunostimulatory moieties.
The patent ensures designing, manufacturing,
pharmaceutical compositions [34].
3. Lipid polymer hybrid particles: The patent by inventor
includes an aqueous core enclosed by an amphiphilic
layer which is further surrounded by a polymeric
matrix. The inner core entrap hydrophilic drug eg.
Nucleic acids proteins, peptides. The polymer layer
is also used to entrap hydrophobic drugs and could
be surrounded by conjugated lipoidal molecules. The
major step is of formulating both polymer and lipid
based nanoparticles with a size range of less than 400
micrometers. An example of formulation is an aqueous
core optionally containing a nucleic acid (e.g., siRNA) is
surrounded by an inner lipid (e.g., EPCl4: 1) layer. The
hydrophobic portions of the inner lipids interact with a
polymeric shell (e. g., PLGA), which encapsulates a drug
(e.g., docetaxel). The polymeric shell is surrounded by
an outer lipid layer that includes one or more lipids
(e.g., lecithin) and a PEGylated lipid [35].
4. Porous nanoparticle supported lipid bilayer
nanostructures: Another patent, provides the
description and formulation of the protocells. These are
nanostructures which contains porous particle core and
enclosed by a lipid bilayer. It was capable to entrapping
more than one component, further, unloading of those
components at the particular target site. These were
found to capable to deliver peptides, antibodies. The
polymer allowed better stability of the protocells. The
protocells including porous nanoparticles had 110nm in
atleast one dimension [36].
5. Nanoparticles with lipid core and polymer shell
structures for protein drug delivery prepared by
nanoencapsulation: The invention relates to the
stabilized nanoparticles involving lecithin playing
role as a component of core structure and enclosed
covering by poloxamer. It referred to the freeze dried
nanoparticles with lecithin, aqueous drug solution and
polaxamer in the presence of a cryoprotectant. These
were also added with some additives for the stabilization
such as emulsifier. Both the lecithin and the polaxamer
with the protein drug were prepared individually. The
polaxamer or a block copolymer is a poly(oxyethylene)-
poly(oxypropylene)-poly(oxyethylene) triblock
copolymer, which is usually called poloxamer [37].
6. Carbohydrate based lipid compositions and
supramolecular structures comprising same: In
this patent, it refer to the exceptional class of the
nanoparticles wherein the glycerol substrate is replaced
with carbohydrate. Zwitter ion, cationic, anionic
carbohydrate based phospholipid was synthesized
and evaluated. The hybrid lipid nanoparticles were
generated with different ingredient of carbohydrate
based phospholipid such as dimyristyl phosphocholine
(DPMC), nucleic acid etc leading to the supramolecular
structures. It was also replaced by polyether, polyester,
polyamine, polyacrylic acid, polysaccharide [38].
7. Targeted and triggered Chitosan lipid core shell
nanoparticles for combination chemotherapy: The
patent is aimed to ensure chitosan lipid polymer hybrid
nanoparticles for the action of two or more anticancer
drugs. It was such designed to evoke drug release at the
target site under the influence of enzyme with a size of
less than 200nm. It was also interacted with transferrin
4. Kasera et al. (2016)
028
Citation: Kasera NK, Sharma PK, Gupta R (2016) Recent Advancement and Patents of the Lipid Polymer Hybrid Nanoparticles. Peertechz J Med Chem Res 2(1):
009-029. DOI: http://dx.doi.org/10.17352/ojc.000005
peptide to counter the transferrin receptors on cancerous
cells. These ultimately under fire the cancer cells with
two or more cancer treating drugs [39].
8. Supramolecular structure biodegradable polymeric
assembly for drug delivery: This invention introduces
a novel drug carrier into a living body consisting of
a highly water-soluble polymer that can carry and
release a drug at a desired rate. It is a supramolecular-
structured biodegradable polymeric assembly that can
release the drug as a purpose of the specific actions
of biodegradation of a diseased body. Characterized
in that the linear polymeric chain compound
threading through the structural cavity of the cyclic
compounds is poly (ethylene glycol), poly (propylene
glycol), polyisobutylene or a block copolymer. A
supramolecular-structured biodegradable polymeric
assembly characterized in that the drug to be combined
with cyclodextrins is a peptide drug [40].
9. Core shell nanoparticles including nucleic acid hydrogel
and method of producing the same: This invention
embodies a functional complex particle prepared by
filling a nucleic acid hydrogel inside a liposome and
a method of producing the core shell nanoparticles.
The invention may have an effect of increasing an
expression of protein factors included in the particle by
incorporating an X-shaped nucleic acid monomer in the
nucleic acid hydrogel. Accordingly, when the core-shell
particle is prepared using the method according to an
embodiment of the invention, an effect of facilitating an
introduction of a genome into the nucleic acid hydrogel
may be obtained, and thereby the core-shell particle may
be used as a protein production platform copying a cell
nucleus, wherein the lipid includes one or more selected
from the group consisting of 1,2-dihexadecanoyl-sn-
glycero-3-phosphoethanolamine, triethylammonium
salt (Texas Red DHPE), cholesterol, 1-palmitoyl-
2-oleoyl-sn-glycero-3-phosphocholine (POPC),
1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1’-rac-
glycerol) (POPG), and mixtures thereof [41].
Conclusion
Lipid polymer hybrid nanoparticles constituting lipids is
carried in the blood plasma in the form of chylomicrons or
micelles. Although, lymphatic system is the route of the lipid
metabolism. From the various studies, it can be extracted that
insertion of cholesterol into the formulation, increases the
half- life of the lipid and decreasing the lipid clearance and
these could further result into the extension of the drug release.
Lipid polymer hybrid nanoparticles on further advancement
can also be used for the therapy of other diseases apart from
the cancer therapy such as diabetes. It can also be used in the
delivery of immunostimulatory agents, genes, hormones etc.
These nanoparticles can be administered by intravenous route
as well as by oral administration by preventing it from enzymal
degradation representing its stealth property.
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