This document provides an overview of targeted drug delivery systems for cancer. It discusses various types of cancer and factors that contribute to cancer development. It then describes challenges with traditional chemotherapy and discusses how targeted therapies can help address issues like dose-limiting toxicity. Various targeted delivery methods are summarized, including use of monoclonal antibodies, immunoliposomes, nanoparticles, and implantable systems. The document also discusses molecular markers that can help guide targeted therapies and provides examples of FDA-approved targeted drugs.
1) Biodegradable polymers are polymers that break down into smaller molecules through mechanisms such as hydrolysis or enzymatic degradation. They include both synthetic polymers like polylactic acid, polyglycolic acid, and polycaprolactone, as well as natural polymers like collagen and albumin.
2) The degradation of biodegradable polymers can occur through either surface or bulk erosion and can be mediated by water, enzymes, or microorganisms. Common mechanisms include cleavage of crosslinks, transformation of side chains, or cleavage of the polymer backbone.
3) Biodegradable polymers find applications as drug delivery systems where they provide localized and sustained release of drugs as well as reduce dosing frequency
Microencapsulation is a process where tiny particles or droplets of a core material are surrounded by a coating to form capsules in the micrometer to millimeter range called microcapsules. Various techniques are used to produce microcapsules including air suspension, pan coating, coacervation, spray drying, solvent evaporation, and polymerization. Microencapsulation offers advantages like taste masking, sustained release, and environmental protection. Some applications of microencapsulation include modified release dosage forms, enteric coatings, and replacement of therapeutic agents.
Liposomes are spherical vesicles composed of lipid bilayers that can encapsulate aqueous content. They are used as drug delivery systems to improve drug solubility, stability, and targeting. Liposomes are prepared using various methods involving dispersion of lipids in aqueous solution. Key components are phospholipids like phosphatidylcholine and cholesterol. Characterization evaluates parameters like size, shape, drug entrapment efficiency, and phase behavior. Liposomes offer benefits like increased drug efficacy and stability but also have challenges like short shelf life and high production costs.
Monoclonal antibodies preparatation and applicatationSUJITHA MARY
Monoclonal antibodies (mAbs) are identical antibodies produced by one type of immune cell that are directed against a specific antigen. They are produced through the fusion of B cells with myeloma cells to form hybridoma cells that can produce identical mAbs. mAbs have various applications including diagnostic uses in assays and imaging, therapeutic uses in cancer treatment and organ transplants, and research uses in protein purification. Their production involves immunizing mice with antigens, fusing spleen cells with myeloma cells, selecting antibody-producing hybridomas, and propagating the selected hybridoma cell lines to produce mAbs.
Colloidal particles ranging in size between 10 & 1000 nm are known as nanoparticles.
SLNs are new generation of submicron sized lipid emulsion where the liquid lipid(oil) has been substituted by a solid lipid.
Example: Capture - Dior
1) Biodegradable polymers are polymers that break down into smaller molecules through mechanisms such as hydrolysis or enzymatic degradation. They include both synthetic polymers like polylactic acid, polyglycolic acid, and polycaprolactone, as well as natural polymers like collagen and albumin.
2) The degradation of biodegradable polymers can occur through either surface or bulk erosion and can be mediated by water, enzymes, or microorganisms. Common mechanisms include cleavage of crosslinks, transformation of side chains, or cleavage of the polymer backbone.
3) Biodegradable polymers find applications as drug delivery systems where they provide localized and sustained release of drugs as well as reduce dosing frequency
Microencapsulation is a process where tiny particles or droplets of a core material are surrounded by a coating to form capsules in the micrometer to millimeter range called microcapsules. Various techniques are used to produce microcapsules including air suspension, pan coating, coacervation, spray drying, solvent evaporation, and polymerization. Microencapsulation offers advantages like taste masking, sustained release, and environmental protection. Some applications of microencapsulation include modified release dosage forms, enteric coatings, and replacement of therapeutic agents.
Liposomes are spherical vesicles composed of lipid bilayers that can encapsulate aqueous content. They are used as drug delivery systems to improve drug solubility, stability, and targeting. Liposomes are prepared using various methods involving dispersion of lipids in aqueous solution. Key components are phospholipids like phosphatidylcholine and cholesterol. Characterization evaluates parameters like size, shape, drug entrapment efficiency, and phase behavior. Liposomes offer benefits like increased drug efficacy and stability but also have challenges like short shelf life and high production costs.
Monoclonal antibodies preparatation and applicatationSUJITHA MARY
Monoclonal antibodies (mAbs) are identical antibodies produced by one type of immune cell that are directed against a specific antigen. They are produced through the fusion of B cells with myeloma cells to form hybridoma cells that can produce identical mAbs. mAbs have various applications including diagnostic uses in assays and imaging, therapeutic uses in cancer treatment and organ transplants, and research uses in protein purification. Their production involves immunizing mice with antigens, fusing spleen cells with myeloma cells, selecting antibody-producing hybridomas, and propagating the selected hybridoma cell lines to produce mAbs.
Colloidal particles ranging in size between 10 & 1000 nm are known as nanoparticles.
SLNs are new generation of submicron sized lipid emulsion where the liquid lipid(oil) has been substituted by a solid lipid.
Example: Capture - Dior
Monoclonal antibody as targeting drug delivery systemsagarwani560
Monoclonal antibodies (Mabs) can be used for targeted drug delivery. Mabs are produced through cell fusion between B cells and myeloma cells, generating hybridomas that secrete antibodies against a specific antigen. This allows production of antibodies that are homogeneous and specific. Mabs can be conjugated to drugs to actively target delivery to sites like tumors, reducing side effects. Targeted delivery using Mabs aims to achieve the desired pharmacological response at selected sites without undesirable interactions elsewhere.
This document discusses targeted drug delivery systems. It defines targeted drug delivery as selectively delivering medication to its site of action to increase concentration in tissues of interest while reducing it in other tissues, improving efficacy and reducing side effects. The document outlines various strategies for targeted delivery including passive, active, ligand-mediated and physical targeting. It also describes several types of targeted delivery systems including liposomes, dendrimers, nanotubes, nanoshells and others. The goal is to achieve the desired pharmacological response at selected sites with minimal side effects.
Smart polymers undergo reversible physical or chemical changes in response to small environmental variations such as temperature, pH, light, or enzymes. Temperature-responsive polymers include shape-memory materials, liquid crystalline materials, and responsive polymer solutions. Polymers like poly(N-isopropylacrylamide) undergo a phase change at a lower critical solution temperature, while some exhibit an upper critical solution temperature. Photo-responsive polymers change properties like conformation or polarity when exposed to light. Magnetically-responsive polymers contain superparamagnetic iron oxide nanoparticles and change properties in the presence of a magnetic field.
This document discusses nanoparticles, including their definition as submicron colloidal structures composed of polymers that are 10-1000nm in size. Nanoparticles can be nanospheres or nanocapsules and are useful for site-specific drug delivery. Some key advantages are achieving maximum drug effects with minimal side effects through active and passive targeting. The document outlines various polymer types used in nanoparticle production and evaluation methods like particle size, surface charge, drug loading efficiency and in vitro drug release.
1. Liposomes are spherical vesicles made of phospholipid bilayers that can encapsulate aqueous content. They range in size from 20nm to micrometers.
2. Liposomes are composed mainly of phospholipids and cholesterol. Commonly used phospholipids include phosphatidylcholine, phosphatidylethanolamine, and dioleoyl phosphatidylcholine. Cholesterol helps stabilize the bilayer structure.
3. Liposomes offer advantages like low toxicity, biodegradability, protection of encapsulated drugs, and improved pharmacokinetics. However, they also have disadvantages such as drug leakage, short half-life, high production costs, and difficulty in large-scale manufacturing
Nanoparticle targeted drug delivery systemBINDIYA PATEL
This document discusses nanoparticles as subnanosized colloidal drug delivery systems ranging from 10-1000 nm in diameter. It defines nanoparticles and describes their basic concept of selectively delivering drugs to target tissues while restricting access to non-target tissues. The document outlines ideal characteristics of nanoparticles and various methods for their preparation, characterization, and evaluation. It provides examples of nanoparticle applications such as cancer therapy, intracellular targeting, vaccines, DNA delivery, and ocular delivery. The document concludes by listing references for further information on nanoparticles.
Electrophoresis is the migration of charged particles through a solution under the influence of an electric field. Biological molecules like proteins, nucleic acids, and carbohydrates can be charged and separated via electrophoresis based on factors like their charge, size, shape, the applied electric field, buffer composition, pH, and interactions with the supporting medium. Tiselius moving boundary electrophoresis uses an optical system to observe the movement of protein boundaries in a U-tube apparatus, allowing for the separation and analysis of protein mixtures.
This document provides information about radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques. It discusses the principles, requirements, methodology, and applications of RIA. Key steps in RIA include radio label production, conjugate preparation, antibody production and characterization, and separation techniques. RIA has applications in pharmaceutical analysis and pharmacokinetic studies. ELISA can be used to detect antigens or antibodies and has advantages of sensitivity and accurate measurement of low analyte levels. Both techniques have widespread uses in fields like immunoassay, drug analysis, and HIV testing.
BIO ELECTRONIC MEDICINE SUB OF M PHARMACY
BIO ELECTRONIC MEDICINE DEVELOPMENT IN DEPENDS ON THEY BY USING BIO ELECTRIC SIGNAL.BY TREATING ASTHMA BP ARTHARITES
This document provides an overview of liposomes as a drug delivery system. It begins by defining liposomes as spherical vesicles composed of lipid bilayers that can encapsulate aqueous volumes. Liposomes were first produced in 1961. The document then discusses the composition of liposomes, including phospholipids and cholesterol as main components. It describes various methods for liposome preparation, such as film hydration, sonication, extrusion, and detergent removal. Characterization techniques are also outlined. In summary, this document introduces liposomes as lipid bilayer structures for drug delivery and encapsulation, and covers their composition, methods of preparation, and characterization.
This document discusses tumor targeting for drug delivery. It begins by defining tumors and the types of cancer. It then discusses the differences between tumor tissue and normal tissue that allow for targeted delivery. The main approaches to tumor targeting discussed are passive targeting, which exploits the enhanced permeability and retention effect, and active targeting using ligands that bind to receptors overexpressed on tumor cells. Examples are given of marketed products that use each approach. Triggered drug delivery is also covered, which releases drugs in response to the unique tumor microenvironment.
Microneedles provide a promising approach for transdermal drug delivery that combines the benefits of hypodermic needle injections and transdermal patches. They are typically hundreds of microns long and can deliver drugs in a minimally invasive and painless manner. Various types of microneedles have been developed including solid, dissolving, and hollow microneedles. They offer advantages over traditional delivery methods such as avoiding first-pass metabolism and providing controlled delivery of large molecules. Microneedles have applications in delivering drugs, vaccines, cosmetics and diagnostics. While they provide benefits, microneedles still need to overcome challenges related to fabrication, drug encapsulation and skin variability.
This document provides an overview of sustained and controlled drug delivery systems (SR and CRDDS). It defines SR and CRDDS and compares their drug release profiles. The advantages include improved bioavailability and compliance while disadvantages include dose dumping and adjustment difficulties. Drugs are selected based on their physicochemical, pharmacokinetic, and pharmacodynamic properties. SR and CRDDS are classified into continuous release, delayed transit-continuous release, and delayed release systems. They are evaluated for properties like drug release and stability. Applications include oral, ocular, transdermal, and colonic delivery. Marketed products of these systems in tablets, capsules, and transdermal forms are also mentioned.
Effective permeation and retention effect [epr effectNeeraj Pandey
The EPR effect allows macromolecular drugs to selectively accumulate and be retained in solid tumors over normal tissues. It exploits the anatomical and physiological differences between tumor and normal vasculature. Tumor blood vessels are defective and permeable, lacking smooth muscle and pericytes. They also have poor lymphatic drainage. This allows nanoparticles and macromolecules to extravasate into tumors and be retained, achieving drug concentrations 10-200 times higher than in normal tissues. Various approaches can potentiate the EPR effect, such as targeting tumor vasculature to increase permeability or reducing tumor cell barriers to enhance penetration and retention of drug delivery systems.
This document summarizes liposomal drug delivery systems (LDDS). It discusses that liposomes are spherical vesicles composed of phospholipid bilayers that can encapsulate both hydrophilic and hydrophobic drugs. Several liposomal drugs have been clinically approved to treat conditions like fungal infections. Liposomes offer advantages like increased drug efficacy, reduced toxicity, and ability to target specific sites. However, they also face challenges like rapid clearance and batch-to-batch variability. The document also outlines various methods for preparing, classifying, and stabilizing liposomes for use as drug carriers.
This document provides an overview of differential thermal analysis (DTA). It begins with a definition of DTA, stating that it is a technique used to identify and analyze the chemical composition of substances by observing their thermal behavior when heated. It then describes the basic principles and instrumentation of DTA. The principles section explains that DTA measures the temperature difference between a sample and reference material as they are heated. Physical changes appear as endothermic peaks while chemical reactions tend to be exothermic. The instrumentation section outlines the key components of a DTA device, including the furnace, sample holders, temperature controller, and recorder. It also describes how DTA works and provides examples of DTA thermograms. The document concludes by discussing
This document provides an overview of dendrimers, which are highly branched, monodisperse polymeric nanoparticles. It discusses the origins and history of dendrimers, methods for synthesizing them including divergent and convergent approaches, their core-shell structure and properties. Applications of dendrimers mentioned include drug delivery, with mechanisms like encapsulation, electrostatic interactions and covalent conjugation. Characterization techniques and examples of dendrimer types like PAMAM are also summarized.
In this slides contains principle and instrumentation of Differential Scanning Calorimeter (DSC).
Presented by: N Poojitha. (Department of pharmaceutics),
RIPER, anantapur.
This document provides an overview of osmotic drug delivery systems. It discusses the basic components and principles of osmosis that osmotic drug delivery systems utilize. The key components discussed include the drug, osmogen, semipermeable membrane, and factors that affect drug release such as solubility, osmotic pressure, delivery orifice size, and membrane type. A variety of osmotic pump designs are also briefly mentioned.
This document discusses two types of immunoassays: radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). RIA was developed in the 1950s and involves competition between labeled and unlabeled antigens for binding with antibodies. The amount of radioactivity measured corresponds to antigen concentration. ELISA is commonly used for initial HIV screening and has advantages over RIA by not requiring radioactive materials. ELISA uses an enzyme-linked antibody for detection and can be performed as either a direct or indirect assay. Both methods have various applications for detecting proteins, antibodies, drugs, and diagnosing infections.
Nanoparticles have potential as drug carriers that fulfill attributes of Ehrlich's "magic bullet" concept by carrying drugs in a stable form to specific disease sites while avoiding non-specific interactions. They can be engineered for active or passive tumor targeting. Active targeting uses ligand-coupled nanoparticles that bind to receptors overexpressed on tumor cells, enhancing drug internalization and treatment efficacy through synergistic effects and bypassing multidrug resistance mechanisms. Passive targeting relies on nanoparticles accumulating in tumors through leaky vasculature via the enhanced permeation and retention effect. Together, active and passive targeting may improve drug delivery for cancer treatment.
Tumors can be benign or malignant. Benign tumors are slow-growing, encapsulated masses that do not metastasize, while malignant tumors are fast-growing, invasive tumors that can metastasize to other parts of the body. Targeted cancer therapies work by interrupting unique molecular abnormalities that drive cancer growth for a particular cancer type. Examples include hormone therapies, signal transduction inhibitors, gene expression modulators, apoptosis inducers, angiogenesis inhibitors, immunotherapies, and toxin delivery molecules. However, cancer cells can become resistant to targeted therapies over time.
Monoclonal antibody as targeting drug delivery systemsagarwani560
Monoclonal antibodies (Mabs) can be used for targeted drug delivery. Mabs are produced through cell fusion between B cells and myeloma cells, generating hybridomas that secrete antibodies against a specific antigen. This allows production of antibodies that are homogeneous and specific. Mabs can be conjugated to drugs to actively target delivery to sites like tumors, reducing side effects. Targeted delivery using Mabs aims to achieve the desired pharmacological response at selected sites without undesirable interactions elsewhere.
This document discusses targeted drug delivery systems. It defines targeted drug delivery as selectively delivering medication to its site of action to increase concentration in tissues of interest while reducing it in other tissues, improving efficacy and reducing side effects. The document outlines various strategies for targeted delivery including passive, active, ligand-mediated and physical targeting. It also describes several types of targeted delivery systems including liposomes, dendrimers, nanotubes, nanoshells and others. The goal is to achieve the desired pharmacological response at selected sites with minimal side effects.
Smart polymers undergo reversible physical or chemical changes in response to small environmental variations such as temperature, pH, light, or enzymes. Temperature-responsive polymers include shape-memory materials, liquid crystalline materials, and responsive polymer solutions. Polymers like poly(N-isopropylacrylamide) undergo a phase change at a lower critical solution temperature, while some exhibit an upper critical solution temperature. Photo-responsive polymers change properties like conformation or polarity when exposed to light. Magnetically-responsive polymers contain superparamagnetic iron oxide nanoparticles and change properties in the presence of a magnetic field.
This document discusses nanoparticles, including their definition as submicron colloidal structures composed of polymers that are 10-1000nm in size. Nanoparticles can be nanospheres or nanocapsules and are useful for site-specific drug delivery. Some key advantages are achieving maximum drug effects with minimal side effects through active and passive targeting. The document outlines various polymer types used in nanoparticle production and evaluation methods like particle size, surface charge, drug loading efficiency and in vitro drug release.
1. Liposomes are spherical vesicles made of phospholipid bilayers that can encapsulate aqueous content. They range in size from 20nm to micrometers.
2. Liposomes are composed mainly of phospholipids and cholesterol. Commonly used phospholipids include phosphatidylcholine, phosphatidylethanolamine, and dioleoyl phosphatidylcholine. Cholesterol helps stabilize the bilayer structure.
3. Liposomes offer advantages like low toxicity, biodegradability, protection of encapsulated drugs, and improved pharmacokinetics. However, they also have disadvantages such as drug leakage, short half-life, high production costs, and difficulty in large-scale manufacturing
Nanoparticle targeted drug delivery systemBINDIYA PATEL
This document discusses nanoparticles as subnanosized colloidal drug delivery systems ranging from 10-1000 nm in diameter. It defines nanoparticles and describes their basic concept of selectively delivering drugs to target tissues while restricting access to non-target tissues. The document outlines ideal characteristics of nanoparticles and various methods for their preparation, characterization, and evaluation. It provides examples of nanoparticle applications such as cancer therapy, intracellular targeting, vaccines, DNA delivery, and ocular delivery. The document concludes by listing references for further information on nanoparticles.
Electrophoresis is the migration of charged particles through a solution under the influence of an electric field. Biological molecules like proteins, nucleic acids, and carbohydrates can be charged and separated via electrophoresis based on factors like their charge, size, shape, the applied electric field, buffer composition, pH, and interactions with the supporting medium. Tiselius moving boundary electrophoresis uses an optical system to observe the movement of protein boundaries in a U-tube apparatus, allowing for the separation and analysis of protein mixtures.
This document provides information about radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques. It discusses the principles, requirements, methodology, and applications of RIA. Key steps in RIA include radio label production, conjugate preparation, antibody production and characterization, and separation techniques. RIA has applications in pharmaceutical analysis and pharmacokinetic studies. ELISA can be used to detect antigens or antibodies and has advantages of sensitivity and accurate measurement of low analyte levels. Both techniques have widespread uses in fields like immunoassay, drug analysis, and HIV testing.
BIO ELECTRONIC MEDICINE SUB OF M PHARMACY
BIO ELECTRONIC MEDICINE DEVELOPMENT IN DEPENDS ON THEY BY USING BIO ELECTRIC SIGNAL.BY TREATING ASTHMA BP ARTHARITES
This document provides an overview of liposomes as a drug delivery system. It begins by defining liposomes as spherical vesicles composed of lipid bilayers that can encapsulate aqueous volumes. Liposomes were first produced in 1961. The document then discusses the composition of liposomes, including phospholipids and cholesterol as main components. It describes various methods for liposome preparation, such as film hydration, sonication, extrusion, and detergent removal. Characterization techniques are also outlined. In summary, this document introduces liposomes as lipid bilayer structures for drug delivery and encapsulation, and covers their composition, methods of preparation, and characterization.
This document discusses tumor targeting for drug delivery. It begins by defining tumors and the types of cancer. It then discusses the differences between tumor tissue and normal tissue that allow for targeted delivery. The main approaches to tumor targeting discussed are passive targeting, which exploits the enhanced permeability and retention effect, and active targeting using ligands that bind to receptors overexpressed on tumor cells. Examples are given of marketed products that use each approach. Triggered drug delivery is also covered, which releases drugs in response to the unique tumor microenvironment.
Microneedles provide a promising approach for transdermal drug delivery that combines the benefits of hypodermic needle injections and transdermal patches. They are typically hundreds of microns long and can deliver drugs in a minimally invasive and painless manner. Various types of microneedles have been developed including solid, dissolving, and hollow microneedles. They offer advantages over traditional delivery methods such as avoiding first-pass metabolism and providing controlled delivery of large molecules. Microneedles have applications in delivering drugs, vaccines, cosmetics and diagnostics. While they provide benefits, microneedles still need to overcome challenges related to fabrication, drug encapsulation and skin variability.
This document provides an overview of sustained and controlled drug delivery systems (SR and CRDDS). It defines SR and CRDDS and compares their drug release profiles. The advantages include improved bioavailability and compliance while disadvantages include dose dumping and adjustment difficulties. Drugs are selected based on their physicochemical, pharmacokinetic, and pharmacodynamic properties. SR and CRDDS are classified into continuous release, delayed transit-continuous release, and delayed release systems. They are evaluated for properties like drug release and stability. Applications include oral, ocular, transdermal, and colonic delivery. Marketed products of these systems in tablets, capsules, and transdermal forms are also mentioned.
Effective permeation and retention effect [epr effectNeeraj Pandey
The EPR effect allows macromolecular drugs to selectively accumulate and be retained in solid tumors over normal tissues. It exploits the anatomical and physiological differences between tumor and normal vasculature. Tumor blood vessels are defective and permeable, lacking smooth muscle and pericytes. They also have poor lymphatic drainage. This allows nanoparticles and macromolecules to extravasate into tumors and be retained, achieving drug concentrations 10-200 times higher than in normal tissues. Various approaches can potentiate the EPR effect, such as targeting tumor vasculature to increase permeability or reducing tumor cell barriers to enhance penetration and retention of drug delivery systems.
This document summarizes liposomal drug delivery systems (LDDS). It discusses that liposomes are spherical vesicles composed of phospholipid bilayers that can encapsulate both hydrophilic and hydrophobic drugs. Several liposomal drugs have been clinically approved to treat conditions like fungal infections. Liposomes offer advantages like increased drug efficacy, reduced toxicity, and ability to target specific sites. However, they also face challenges like rapid clearance and batch-to-batch variability. The document also outlines various methods for preparing, classifying, and stabilizing liposomes for use as drug carriers.
This document provides an overview of differential thermal analysis (DTA). It begins with a definition of DTA, stating that it is a technique used to identify and analyze the chemical composition of substances by observing their thermal behavior when heated. It then describes the basic principles and instrumentation of DTA. The principles section explains that DTA measures the temperature difference between a sample and reference material as they are heated. Physical changes appear as endothermic peaks while chemical reactions tend to be exothermic. The instrumentation section outlines the key components of a DTA device, including the furnace, sample holders, temperature controller, and recorder. It also describes how DTA works and provides examples of DTA thermograms. The document concludes by discussing
This document provides an overview of dendrimers, which are highly branched, monodisperse polymeric nanoparticles. It discusses the origins and history of dendrimers, methods for synthesizing them including divergent and convergent approaches, their core-shell structure and properties. Applications of dendrimers mentioned include drug delivery, with mechanisms like encapsulation, electrostatic interactions and covalent conjugation. Characterization techniques and examples of dendrimer types like PAMAM are also summarized.
In this slides contains principle and instrumentation of Differential Scanning Calorimeter (DSC).
Presented by: N Poojitha. (Department of pharmaceutics),
RIPER, anantapur.
This document provides an overview of osmotic drug delivery systems. It discusses the basic components and principles of osmosis that osmotic drug delivery systems utilize. The key components discussed include the drug, osmogen, semipermeable membrane, and factors that affect drug release such as solubility, osmotic pressure, delivery orifice size, and membrane type. A variety of osmotic pump designs are also briefly mentioned.
This document discusses two types of immunoassays: radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). RIA was developed in the 1950s and involves competition between labeled and unlabeled antigens for binding with antibodies. The amount of radioactivity measured corresponds to antigen concentration. ELISA is commonly used for initial HIV screening and has advantages over RIA by not requiring radioactive materials. ELISA uses an enzyme-linked antibody for detection and can be performed as either a direct or indirect assay. Both methods have various applications for detecting proteins, antibodies, drugs, and diagnosing infections.
Nanoparticles have potential as drug carriers that fulfill attributes of Ehrlich's "magic bullet" concept by carrying drugs in a stable form to specific disease sites while avoiding non-specific interactions. They can be engineered for active or passive tumor targeting. Active targeting uses ligand-coupled nanoparticles that bind to receptors overexpressed on tumor cells, enhancing drug internalization and treatment efficacy through synergistic effects and bypassing multidrug resistance mechanisms. Passive targeting relies on nanoparticles accumulating in tumors through leaky vasculature via the enhanced permeation and retention effect. Together, active and passive targeting may improve drug delivery for cancer treatment.
Tumors can be benign or malignant. Benign tumors are slow-growing, encapsulated masses that do not metastasize, while malignant tumors are fast-growing, invasive tumors that can metastasize to other parts of the body. Targeted cancer therapies work by interrupting unique molecular abnormalities that drive cancer growth for a particular cancer type. Examples include hormone therapies, signal transduction inhibitors, gene expression modulators, apoptosis inducers, angiogenesis inhibitors, immunotherapies, and toxin delivery molecules. However, cancer cells can become resistant to targeted therapies over time.
This document discusses drug targeting and various drug delivery systems for targeted drug delivery. It describes how drug targeting aims to selectively deliver drugs to the site of action and not to non-target tissues. Various polymer-based particulate carriers for targeted drug delivery are then discussed, including liposomes, microspheres, nanoparticles, and polymeric micelles. The document provides details on the composition, preparation techniques and applications of these particulate carriers. Key advantages and challenges of different targeted drug delivery approaches are also summarized.
This document discusses targeted drug delivery using nanoparticles and liposomes. It provides an introduction to nanoparticles and describes different types including nanospheres and nanoencapsules. It then discusses various natural and synthetic polymers used to prepare nanoparticles, as well as preparation techniques such as solvent evaporation and high-pressure homogenization. The document also briefly introduces solid lipid nanoparticles and describes their advantages. Purification techniques for nanoparticles like dialysis and freeze drying are also mentioned.
This document discusses epidermal growth factor receptor (EGFR) inhibitors for the treatment of non-small cell lung cancer. It provides background on EGFR expression in various cancers and the role of EGFR in tumor growth. It describes various EGFR inhibitors including cetuximab, gefitinib and erlotinib. It summarizes several clinical trials that evaluated these drugs as monotherapy or in combination with chemotherapy. It discusses ongoing research questions around patient selection, combination/sequencing of therapies, and use of EGFR inhibitors in other cancer types.
Bosutinib is a tyrosine kinase inhibitor approved by the FDA and EMA in 2012-2013 for the treatment of chronic myelogenous leukemia. It suppresses migration and invasion of breast cancer cells by inhibiting signaling pathways controlling tumor cell motility and invasion. Bosutinib comes in 100 mg and 500 mg doses and works by blocking certain tyrosine kinases.
Defining Chemical Target and Pathway Toxicity Mechanisms with Primary Human C...BioMAP® Systems
The document discusses the challenges of predictive toxicology due to biological complexity and the potential role of cell-based assays. It describes the BioMAP platform which uses primary human cell systems to model disease biology and responses to drugs and chemicals. BioMAP profiles compound effects on multiple biomarkers and can identify toxicity mechanisms and pathways. However, data analysis is complicated by concentration effects, cytotoxicity, and heterogeneous assay readouts. Specialized approaches are needed to analyze the complex, multiparameter data generated by these human cell-based systems.
Role of stat3 protein & thelper 17 cell in psoriasis development by yousryM.YOUSRY Abdel-Mawla
This document discusses the role of STAT3 and Th17 cells in the development of psoriasis. It describes how STAT3 signaling regulates the differentiation of naive T cells into Th17 cells through the production of cytokines like IL-6, IL-21, and IL-23. Th17 cells secrete pro-inflammatory cytokines like IL-17 and IL-22 that contribute to psoriasis by stimulating keratinocyte growth and activation. The overexpression of Th17 cells and cytokines in the skin is thought to play a key role in the pathogenesis of psoriasis.
Signal Transducer & Activator of Transcription (STAT)-3 plays an important role in psoriasis. STAT3 is activated in epidermal keratinocytes in human psoriatic lesions and links activated keratinocytes to immune cells required for the development of psoriasis. Transgenic mice with keratinocytes expressing a constitutively active form of STAT3 (K5.Stat3C mice) develop a skin phenotype resembling psoriasis when exposed to wounding. The development of psoriatic lesions in these mice requires cooperation between STAT3 activation in keratinocytes and activated T cells. Targeting STAT3 may be a potential therapeutic approach for treating psoriasis.
PRESENTATION ON JANUS KINASE INHIBITORS IN TREATMENT OF MPN'SSamaira Mujeeb
The document discusses Janus kinase 2 (JAK2) inhibitors as a potential treatment for myeloproliferative diseases. It describes how the discovery of activating JAK2 mutations in patients with myeloproliferative neoplasms led pharmaceutical companies to develop JAK2 selective inhibitors. JAK2 inhibitors effectively reduce JAK2 phosphorylation of STAT5 and cell survival in JAK2 activated cells. Patients treated with JAK2 inhibitors experience reductions in spleen size and improvements in symptoms. The document examines different scaffolds that have been used to develop JAK2 inhibitors and some inhibitors currently in clinical trials, such as CEP-701 and AZD1480.
use of omega-transaminase enzyme chemistry in the synthesis of JAK2 kinase in...Kashif Haider
use of enzyme chemistry is discussed with example of drugs in there synthesis. drugs in clinical trail of jak-2 enzyme inhibitors , and different scheme for enzyme synthesis is covered.
This document summarizes several presentations from the 2014 American Society of Hematology (ASH) Annual Meeting regarding chronic myeloid leukemia (CML), multiple myeloma, and lymphoma. For CML, early results from the Phase III EPIC trial found that ponatinib resulted in deeper and more rapid responses compared to imatinib but with increased toxicity. Subset analyses of the PACE trial demonstrated that early molecular responses to ponatinib correlated with improved long-term outcomes. For multiple myeloma, updated criteria were presented for diagnosis. The Phase III FIRST trial showed that continuous lenalidomide and dexamethasone improved progression-free survival compared to fixed-duration regimens or melphalan, prednisone
This document summarizes clinical trial results of the oral ALK inhibitor crizotinib (PF-02341066) in patients with ALK-positive non-small cell lung cancer. The trial showed that crizotinib had significant clinical activity in ALK-positive NSCLC patients, with an objective response rate of 57% and disease control rate of 87%. The median progression-free survival was 10 months for these patients. In contrast, patients with ALK-negative NSCLC did not respond to crizotinib. These results provide evidence that crizotinib is an effective targeted therapy for patients with ALK-positive NSCLC.
Crizotinib is a c-MET inhibitor that has demonstrated potent inhibitory activity against ALK fusion cells. The document discusses clinical trials of crizotinib in patients with ALK-positive non-small cell lung cancer (NSCLC). Results from Phase I and II trials showed an objective response rate of 57% and disease control rate of 87% with crizotinib. Current Phase II and III trials are further evaluating the efficacy and safety of crizotinib compared to standard chemotherapy in ALK-positive NSCLC patients.
This document discusses the pathogenesis of psoriasis. It notes that psoriasis is one of the most common human afflictions, affecting 25 million people in Europe and North America. It is caused by abnormal growth and differentiation of keratinocytes, and is reversible with appropriate treatment. Genetics and immune system activation also play a role. Recent research has provided insights into the role of the immune system and genetic factors, and psoriasis is now considered a model for other chronic inflammatory diseases. Novel immunotherapies targeting cytokines like TNF have been approved for treatment of severe psoriasis based on clinical studies demonstrating their efficacy.
The document summarizes the Signal Transducer and Activator of Transcription (STAT) protein family, with a focus on STAT3 and its role in psoriasis. It describes how STAT proteins are activated downstream of cytokine and growth factor receptors via phosphorylation by Janus kinases (JAKs). STAT3 in particular is activated by cytokines like IL-6 and plays roles in processes like acute phase response, cell growth, and embryonic development. Aberrant STAT3 activation has been implicated in conditions like psoriasis and cancer.
This webinar covered oral chemotherapy options for colorectal cancer. The speaker discussed commonly used intravenous drugs as well as the two FDA-approved oral options: capecitabine and regorafenib. Capecitabine is an oral prodrug of 5-FU that is used as an alternative to intravenous 5-FU for stages II-IV disease. Regorafenib is used for metastatic colorectal cancer that has progressed on all standard therapies. The talk outlined how the drugs work, their administration schedules, common side effects, and factors to consider when determining if oral chemotherapy is appropriate. It emphasized that oral chemotherapy still requires vigilance regarding side effects and medication adherence.
01.13.09: Chronic Myeloid Leukemia and other Myeloproliferative Neoplasms (MPNs)Open.Michigan
Slideshow is from the University of Michigan Medical
School's M2 Hematology / Oncology sequence
View additional course materials on Open.Michigan: openmi.ch/med-M2Hematology
Chemotherapy is the main treatment for disseminated cancers. It involves using multiple drugs in cycles to target rapidly dividing cancer cells. Common drugs include alkylating agents, antimetabolites, microtubule inhibitors, and monoclonal antibodies. Combination chemotherapy aims to maximize responses while avoiding overlapping toxicities. Doses are based on body surface area and adjusted for individual factors. Treatment intervals allow time for normal tissues to recover between cycles. Toxicities include myelosuppression, nausea/vomiting, and alopecia. Response is evaluated based on tumor shrinkage or progression.
Monoclonal antibodies are monospecific antibodies produced by identical immune cells that are clones of a single parent cell. They bind to the same epitope or antigen. There are several types of monoclonal antibodies including murine, chimeric, humanized, and human antibodies. Monoclonal antibodies have various applications in hematology including as therapeutics for cancers, autoimmune disorders, and transplant rejection by blocking molecular targets, delivering cytotoxic compounds to tumors, or acting as signaling molecules. They can also be used diagnostically in tests like ELISA and immunohistochemistry. Common adverse effects of monoclonal antibodies include infusion reactions, immunosuppression, and increased risk of infection.
Application of Proteomic Science and Immunotherapeutics.pptxShraddhaRaut43
This presentation will give you overall information about the application in Proteomic Science and Immunotherapeutics. It covers Proteomics, Genomics, Metabolomics, Functionomics, Nutrigenomics and Types of Immunotherapeutics, Humanized Antibody Therapy, Immunotherapeutics in Clinical Practice.
1. Solid cancer tumors generally have a low growth fraction and thus respond poorly to chemotherapy, often requiring surgery for removal. Disseminated cancers generally have a high growth fraction and often respond well to chemotherapy.
2. There are several classes of chemotherapeutic agents that work through different mechanisms such as alkylating DNA, inhibiting synthesis of DNA/RNA precursors, or inhibiting microtubule polymerization. Combination chemotherapy is often used to increase effectiveness.
3. Dosage must be modified based on toxicity monitoring like myelosuppression as measured by absolute neutrophil count and platelet count to minimize risks of side effects. Preventative measures and dose modifications can manage toxicities from chemotherapy.
This document summarizes cancer chemotherapy and the various classes of chemotherapeutic drugs. It describes the mechanisms of action, indications, and side effects of alkylating agents, antimetabolites, plant alkaloids, antibiotics, and other classes of drugs. The principles of cancer chemotherapy are to arrest tumor progression by causing cytotoxicity or apoptosis in cancer cells, often targeting DNA or metabolic pathways essential for cell replication. Drugs are generally used in combination to achieve maximal cell killing while remaining within a tolerable toxicity range.
Targeted drug delivery systems aim to selectively deliver drugs to predefined targets in the body while restricting access to non-target tissues to minimize toxicity and maximize therapeutic effects. This is achieved through three common approaches - incorporating drugs into carriers, altering drug structure at the molecular level, or controlling drug input to ensure programmed biodistribution. Ideal carriers can cross anatomical barriers, be recognized and internalized selectively by target cells, and release the drug intracellularly. Biological processes involved in drug targeting include cellular uptake, transport across barriers, extravasation from blood vessels, and lymphatic uptake.
This document summarizes a lecture on tumor targeted drug delivery systems. It discusses how traditional chemotherapy has serious side effects and how targeted drug delivery aims to specifically deliver drugs to tumor cells to minimize side effects. It covers the enhanced permeability and retention effect that enables passive targeting of drugs to tumors. It also discusses active targeting using ligands that bind to receptors overexpressed on tumor cells and vasculature. Examples are given of nanoparticles, antibodies, and small molecules that have been used for targeted delivery. The principles of passive, active, and triggered targeted delivery are explained.
This document discusses principles of chemotherapy and classification of anticancer drugs. It begins by defining cancer and its differences from normal cells. The main principles of chemotherapy discussed are the cell kill hypothesis of Skipper and the Norton Simon hypothesis. It then covers classification of anticancer drugs based on cell cycle specificity and mechanism of action. Specific drug classes discussed in detail include alkylating agents, antimetabolites, antibiotics, and cisplatin.
the presentation include the different type of mechanism used by cancer cells to protect them from anticancer agents lead to produce resistance. the slide include definition of cancer as per WHO, type of tumors, treatment of cancer, goal of treatment, problem associated with chemotherapeutic agents, need of studing mechanisms of resistance for anticancer agents, resistance, different mechanism of drug resistance, epigenetics, drug efflux, drug inactivation, DNA damage repair, drug target alteration and cell death inhibitiond
Cancer chemoprevention uses natural or laboratory-made substances to prevent cancer from developing. It is typically used by people at higher risk of cancer, such as those with a family history or previous cancer. Some chemopreventive agents studied include tamoxifen, raloxifene, aspirin and other NSAIDs. While chemoprevention may lower cancer risk, it also carries risks of side effects that must be weighed against the individual's cancer risk. Clinical trials test chemopreventive agents' safety and efficacy in delaying or preventing cancer. Targeted drug delivery seeks to concentrate medication in tissues of interest while reducing side effects by specifically targeting cancer cells over normal cells. Strategies include passive,
This document discusses targeted cancer therapy. It begins with an introduction to cancer classification and targeted therapy. It then discusses epidemiology, signs and symptoms, and risk factors of cancer. It describes the goals and challenges of targeted therapy development. Targets for targeted therapy include monoclonal antibodies and small molecule inhibitors that target proteins involved in cancer signaling pathways. Treatment involves administration of targeted drugs through intravenous methods. Side effects can include skin, gastrointestinal and blood problems. Limitations include cancer cells developing resistance. Present therapies also include immunotherapy and nanotechnology.
This document discusses targeted cancer therapy. It begins with an introduction to cancer classification and targeted therapy. It then discusses the epidemiology, signs and symptoms, and risk factors of cancer. It describes the goals and challenges of targeted therapy development. Targets for targeted therapy include monoclonal antibodies and small molecule inhibitors that target proteins involved in cancer signaling pathways. Treatment involves targeted drugs administered through pills or IV. Side effects and limitations of targeted therapy are also discussed. The document concludes that targeted therapies provide a more selective treatment approach compared to chemotherapy.
This document discusses targeted cancer therapy. It begins with an introduction to cancer classification and targeted therapy. It then discusses the epidemiology of cancer in India, signs and symptoms, and risk factors. It describes the goals and challenges of targeted therapy development. Targets for targeted therapy include monoclonal antibodies and small molecule inhibitors that target proteins involved in cancer signaling pathways. Treatment involves administration of targeted drugs through pills or IV. Side effects and limitations of targeted therapy are also discussed. The document concludes that targeted therapies provide more selective treatment compared to chemotherapy.
This document discusses targeted cancer therapies and their mechanisms of action. It outlines 10 hallmarks of cancer and describes targeted drugs that inhibit specific proteins and pathways involved in cancer growth. These targeted drugs include small molecule tyrosine kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, and proteosome inhibitors. Examples are provided of targeted therapies used to treat cancers like chronic myeloid leukemia, lung cancer, breast cancer, and multiple myeloma. Potential side effects of targeted therapies are also mentioned.
1. The document discusses various approaches for targeted drug delivery to tumors, including passive targeting exploiting the enhanced permeability and retention (EPR) effect, active targeting using ligands that bind to receptors overexpressed on tumor cells, and physical targeting using stimuli-responsive nanoparticles and external forces like magnets and ultrasound.
2. Two main barriers to effective tumor targeting are heterogeneous blood flow within tumors and overexpression of drug efflux transporters in tumor cells.
3. Common ligands for active targeting discussed include albumin, vitamins like folate, transferrin, lectins, and peptides; while physical approaches include pH-, temperature-, or redox-sensitive nanoparticles and magnetic or ultrasound-guided targeting.
Oncology treatment of cancer: Chemotherapy.pptxRinkupatel55
it help to gain the knwoledge about the cancer treatment about the chemotherapy. in also provide the knowledge regarding criteria for the selection of chemo drug, route, dose, team, preparation of drug, and protection from the side effect of the chemotherapy during the drug prepartion & person itself.
This document discusses immunopotentiation and immunosuppression. It describes three ways to potentiate the immune system: vaccination, adjuvants, and lymphokines. Adjuvants work by affecting antigen presentation or stimulating macrophages. Common adjuvants include Freund's incomplete adjuvant, liposomes, muramyldipeptide, levamisole, and isoprinosine. Lymphokines that can be used include interferons and interleukins. The document also discusses general immunosuppression therapies like cytotoxic agents, glucocorticoids, cyclosporine, tacrolimus, and rapamycin, as well as specific therapies such as monoclonal antibodies and blocking co-stimulatory signals to induce T cell anergy
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
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• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of the 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 lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
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. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Top 10 Best Ayurvedic Kidney Stone Syrups in India
targeted dds for cancer
1. TARGETED DRUG DELIVERY
SYSTEM FOR CANCER
PRESENTED BY
Neha singh
M.pharm 1 yr.
GUIDED BY
V.B pokharkar
Hod
Pharmaceutics
1
2. WHAT IS CANCER?
• Division – uncontrolled cell division
• Growth – formation of a lump (tumour) or large numbers of
abnormal white cells in the blood
• Mutation – changes to how the cell is viewed by the immune
system
• Spread – ability to move within the body and survive in another
part
3. TYPES OF CANCER
• Carcinomas
• Sarcomas
• Lymphomas
• Leukaemias
• Adenomas
• Often prefixed by the specific cell
14. TUMOR PHYSIOLOGY & EPR EFFECT
• Cancerous growth feeds on the existing supply of blood and nutrients. As the
tumor develops, it can develop it’s own blood vessels.
• The blood vessels developed, are often leaky and porous .
• Interstitial pressure inside the tumor is much higher when compared to the
normal cell and viscosity of blood in tumor is much higher –- slower drug
migration .
• Enhanced Permeability and Retention ( EPR ) effect is the property by
which certain sizes of molecules (typically liposomes, nanoparticles, and
macromolecular drugs) tend to accumulate in tumor tissue much more than
they do in normal tissues.
15. Erb-B1
HER1
EGFR
Erb-B2
HER2
neu
Erb-B3
HER3
The HER Family of Receptors
Tyrosine
kinase
domain
Ligand-
binding
domain
Erb-B4
HER4
TGF-α
EGF
Epiregulin
Betacellulin
HB-EGF
Amphiregulin Heregulin
Heregulin (neuregulin-
Epiregulin
HB-EGF
Neuregulins-3, -4
No ligand-
binding
activity*
Ligands
*HER2 dimerizes with other members of the HER family.
Roskoski. Biochem Biophys Res Commun. 2004;319:1.
Rowinsky. Annu Rev Med. 2004;55:433.
18. TREATMENT OPTIONS FOR CANCER
SURGERY
• Surgery: before 1955
• Radiotherapy: 1955-1965
• Hyperthermia: 1958-1967
• Chemotherapy: after 1965
• Immunotherapy and Gene therapy
• The design of tumor specific delivery of chemotherapeutic agents is a
means, to address the issues of the dose-limiting toxic side effects of
these agents, by enhancing the fraction of dose actually reaching the
tumor while, reducing the amount of drug that reaching the non-
targeted organs.
19. Issues with traditional chemotherapy
• Act on all rapidly dividing cells
- non-selective
- toxic to normal cells
- often IV treatments
- finite number of cycles
21. Chemotherapy
Two basic types of agents are recognized
1. Cell Cycle Specific Agents
2. Cell Cycle Nonspecific A gents
Cell Cycle Specific Agents : Act during a specific phase of
the cell cycle –
• S Phase Specific Drug: Anti metabolites, Topoisomerase
Inhibitors
• M Phase Specific Drug: Vinca Alkaloids, Taxanes –
• G2 Phase Specific Drug: Bleomycin
Cell Cycle Nonspecific A gents: Active throughout the cell
cycle –
• Alkylating Agents
• Platinum Compounds
• Antibiotics
22. TARGETED THERAPIES
• Targeted cancer therapies block the growth and spread of cancer by
interfering with specific molecules involved in tumour growth and
progression
Mechanisms of action of targeted therapies
• Interfere with cell growth signalling
• Interfere with tumour blood vessel development
• Promote specific death of cancer cells
• Stimulate the immune system to destroy cancer cells
• Deliver toxic drugs to cancer cells
23.
24. MOLECULAR MARKERS
Gene Cancer Drug
KRAS Colorectal Cetuximab
BRAF Melanoma Vemurafenib
EGFR NCSLC Gefitinib and erlotinib
HER2 Breast Trastuzumab
CKIT GIST Imatinib
25. Role of molecular markers
• Early detection/diagnosis
• Prognosis
• Prediction of toxicity, response, relapse
26. Methods developed to enhance specificity of
chemotherapeutic agents
• First order targeting
• Second order targeting
• Third order targeting
• Passive targeting
• Active targeting
• Physical targeting
27. Anti neoplastic agents can be formulated as…
• Pro-drugs
• Simple Soluble Macro Molecular Systems
• Soluble Synthetic Polymer Systems
• Polymer–Drug Conjugates
• Complex Particulate Multicomponent Systems
28. PRODRUG - Challenging factors
1. Requires an activatable version of the drug, and research in
its development is comparable in cost to drug development.
2. The technology does not necessarily place the drug where it
is needed .
• This may be improved by a targeting carrier system.
29. GLYCOPROTEINS
• The family of glycoproteins includes many enzymes, acute
phase reactant proteins and plasma proteins.
• Mannose, galactose and sialic acid are the principle sugars
that form the carbohydrate components of this simple
macromolecules and tend to confer receptor specificity .
• Use of glycoproteins as a delivery system for antineoplastic
diseases is attractive conceptually due to the targeting
specificity afforded by the ligand - receptor interaction
principle.
30.
31. MONOCLONALANTIBODIES
• Monoclonal antibodies are very specific to their immunological
ligands and are thus very appealing drug carriers.
• Monoclonal antibodies have been coupled to cytotoxic anti cancer
agents such as doxorubicin and the carrier substrate dextran. The
Mabs used in these formulations were directed in theory against
epitopes found only on cancer cells . Antibodies tend to be very
confirmationally stable and usually retain their binding specificity
when combined with other molecules.
34. BISPECIFIC ANTIBODIES
• In carcinoma patients the combination treatment of IL-2 and Bis-
1F bispecific antibody directed against epithelial glycoprotein -2
and TcR/CD3 complex on T-Lymphocytes elicited an immune
response measured by elevated plasma levels of TNF- α and
interferon – γ . Through cross linking of T-cell receptor and CD3
complex on the cytotoxic T-lymphocytes and epithelial
glycoprotein-2 on the target cell , the lymphocyte tends to be
capable of actively lysing the target cells .
35.
36. ANTIBODY DIRECTED ENZYME- PRO DRUG
THERAPY (ADEPT )
• The need for antibody internalization, which is one of the problems
associated with immunoconjugates is a addressed in this
strategy, known as Antibody directed enzyme- pro drug therapy
(ADEPT).
• Enzymosomes are liposomal constructs engineered to provide a mini
bio environment . Enzymes are covalently immobilized or coupled to
the surface of liposomes, therefore, when a non toxic product is
administered simultaneously, it is converted by the immobilized
enzyme to a potent anti-tumor agent in the vicinity of tumor cell lines.
37.
38. IMMUNOTOXIN CONJUGATE
• Toxins are molecules that inactivate Viral cytosolic components
of the protein synthesis machinery in catalytic manner.
• Reaching cytosol is the major requirement.
• Immuno-toxins are the conjugates of antibodies (Mab)/ (Fab)
fragments and toxins in which the cell binding moieties of the
toxins are replaced by the binding specific chain of Ab.
39.
40. SOLUBLE SYNTHETIC POLYMER SYSTEMS
• The synthetic polymeric carriers are large enough to avoid filtration and
removal by the kidneys but small enough to avoid trapping by the liver and
spleen.
• Many natural and synthetic biodegradable polymers have been investigated
as implants, microcapsules, micro particles and nanocapsules in order to
achieve prolonged release and targeting of a variety of drugs.
• Apart from targeting, the backbone of a polymeric carrier molecule provides
both controlled, sustained release pattern and a means of protecting the drug
form the physiological environment.
41. DESIGN OF POLYMER CONJUGATES
POLYMER
• Should degrade into non-toxic, non immunogenic, water soluble
metabolites that are eliminated easily via renal filtration but be
of sufficiently high molecular weight to allow entrapment in the
tumor by EPR effect. E.g.: Dextrin (2000-55,000) Poly glutamic
acid (30,000 -60,000)
• Polymer should possess functional groups which are amenable
to conjugation with a drug directly or through a linker.
• Polymer should possess high drug carrying capacity.
42. COMPLEX PARTICULATE MULTI-
COMPONENT SYSTEMS
• Liposomes
• Niosomes
• Nanoparticles
• Cells as carriers
• Microspheres
• Magnetic microspheres
• Emulsions
• Implantable drug delivery systems
43.
44. LIPOSOMES
• Targeting strategies using liposomes can be designed
as: Natural targeting of conventional liposomes.
Long circulatory liposomes (Stealth liposomes)
Ligand mediated targeting.
45. STERICALLY STABILIZED LIPOSOMES
• It avoid scavenging through receptor mediated uptake by
mononuclear phagocytic cells of RES rich organs. A fraction of
the lipids present, have a polyethylene glycol polymer bound to
their head groups. This polymer binds a lot of water creating a
water cloud around the liposome, which hides it from the immune
system and provide long circulatory behavior . Hence the
name, Stealth liposomes.
46. Liposome targeting to tumors using vitamin
and growth factor receptors
Advances in liposome technology have resulted in the development of
ligand targeted liposomes capable of selectively increasing the efficacy
of carried agents against receptor bearing tumor cells.
Receptors for vitamins and growth factors have become attractive targets
for ligand-directed liposomal therapies due to their high expression
levels on various forms of tumor and their ability to internalize after
binding to the liposomes conjugated to receptors’ natural ligands
(vitamins).
47. Release of drug from liposomes…A Constraint ?
• The design of liposomes can be such that, they can become
leaky a few degrees above the body temperature hence letting
the encapsulated material flow out. By tuning the lipid
composition to become leaky at a certain temperature above
the body temperature.
• it is possible to heat the tumor locally by either
microwave, ultrasound or radio-frequency radiation resulting
in a very fast release of the anti-cancer drug, typically a
million times faster than from conventional liposomes.
48. IMMUNOLIPOSOMES
• Immunoliposomes are generated by conjugating antibodies
either directly to lipid bilayer of liposomes in presence or
absence of PEG chains (type I immunoliposomes) or to the
distal end of the PEG chain (type II immunoliposomes).
• Immunoliposomes, make use of use of hyperthermia.
• Liposomal systems appear to be the most promising carrier
systems, for photo sensitizers in the photodynamic therapy of
tumors agnetic field for the induced release of it’s contents
49. NANOPARTICLES
• The loading of drug into ultrafine colloidal particles in the
nanometer size range (10-1000nm)is done, for optimization of
drug delivery to the desired site with the either the drug
encapsulated, dissolved, adsorbed or covalently attached.
• They can be prepared using natural hydrophilic polymers.
• They can entrap various agents in stable and reproducible fashion.
• Stabilizers such as dextran and its derivatives can be incorporated
into nanoparticle surface to modify it’s surface characteristics.
50. SOLID IMPLANTS :
• Cylindrical monolithic devices of mm or cm dimensions, implanted
by a minor surgical incision or injected through a large bore needle
into subcutaneous or intra muscular tissue .
• The drug in implants may be dissolved or dispersed or embedded in a
matrix of polymers.
• Implantable drug-delivery systems can detect chemical signals in the
body and release appropriate therapeutic dosages for treatment with
the help of biosensors .
• Improved control of drug levels at the specific site of action is
possible, for prolonged duration with significantly small dose.
51. IN-SITU FORMING IMPLANTS :
• In-situ gels consists of biodegradable polymers dissolved in a
biocompatible carrier ( DMSO or NMP ). When the liquid
polymer system is placed in the body, it solidifies upon contact
with aqueous body fluids to form a solid implant. The gel-
matrix, thus formed will release the incorporated drug slowly
over a period of weeks to months, and ultimately biodegrade
depending on the composition used
52. INTRA-TUMORAL DRUG DELIVERY
• The concept of administration of drug directly into the tumor arise
from the non uniform and in adequate accumulation of drug or drug
carrier in the tumor.
• Prodrug approach has been successfully utilized for intra tumoral
chemotherapy for a variety of drugs. Mitomycin C, conjugated with
dextran and subcutaneously implanted in B 16 melanoma, resulted in
reduction in tumor growth.
• It can also be optimized using polymeric implants . Cisplatin-Collagen
matrix, Vinblastine-Collagen matrix, Methotrexate-Polylactide
implant, all have resulted in suppression of tumor.
53. CHEMOEMBOLIZATION
• Embolization is widely acknowledged form of endovascular therapy.
• It consists of delivering an embolic material locally through a catheter
that has been previously inserted in the vessels supplying the
pathological area.
• Chemoembolization involves the selective arterial embolization of a
tumor together with a simultaneous or subsequent local delivery of
chemotherapeutic agents. Microcapsule bound intra-arterial
chemotherapy has the greatest potential in treating most of the tumors.
54. Summary of targeted therapy actions
Mechanism Drug
Interfere with cell growth signalling Erlotinib, Gefitinib, Crizotinib
Interfere with tumour blood vessel
development
Bevacizumab, Pazopanib
Promote specific death of cancer cells Olaparib
Stimulate the immune system to
destroy cancer cells
Ipilimumab
Deliver toxic drugs to cancer cells Trastuzumab emtansine
55. CANCER VACCINES
• Prophylactic vaccines e.g. Gardasil®, Cervarix®
• Therapeutic vaccines:
- delay or stop cancer cell growth
- cause tumour shrinkage
- prevent cancer from recurring
- eliminate cancer cells not killed by other forms of treatment
56. PROVENGE® VACCINE
• Licensed for metastatic prostate cancer in USA
• Designed to stimulate an immune response by T-cells
to prostatic acid phosphatase, an antigen found on
most prostate cancer cells
57. Vaccines in development...
• Telo Vac: immune response against the protein telomerase
which is widely expressed in pancreatic cancer
• IMA901 in combination with sunitinib in renal cell carcinoma
to see if overall survival is improved
• TroVax stimulates the immune system to destroy cancer cells
that express the 5T4 tumour antigen, which is present in
approximately 85% of solid tumours
58. IMPACT OF TARGETED THERAPIES
• Personalised medicine
- given until progression
- additional to existing therapy
- extending life
- improving quality of life