Targeting methods introduction preparation and evaluation: NanoParticles & Liposomes: Types, preparation and evaluation
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This document provides information on molecular pharmaceutics and targeting methods, including nanoparticles and liposomes. It discusses various targeting strategies such as passive, active, inverse and ligand-mediated targeting. Nanoparticles and liposomes are described as carrier systems for targeted drug delivery. The key preparation techniques for nanoparticles include solvent evaporation, double emulsification, emulsions-diffusion and nano precipitation. Nanoparticles are evaluated based on parameters like yield, drug content, particle size, shape, zeta potential and thermal analysis. Targeted drug delivery aims to increase drug concentration at disease sites and reduce side effects.
Targeting methods introduction preparation and evaluation: NanoParticles & Liposomes: Types, preparation and evaluation
- 1. (M.PHARM. Pharmaceutics) 2nd Semester MOLECULAR PHARMACEUTICS – MPH 201 T Targeting Methods: Introduction preparation and evaluation, Nano Particles & Liposomes: Types, preparation and evaluation By SURYAKANT VERMA Assistant Professor, Department of Pharmaceutics,
- 2. CONTENTS 1. Targeting methods • Introduction 2. Nanoparticles • Types • Preparation • Evaluation 3. Liposomes • Preparation • Evaluation • Applications
- 3. TARGETING METHODS:- A special form of drug delivery system where the pharmacologically active agent or medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells. Targeted drug delivery implies for selective and effective localization of pharmacologically active moiety at pre identified (preselected) target in therapeutic concentration, while restricting its access to non-target normal cellular linings, thus minimizing toxic effects and maximizing therapeutic index. INTRODUCTION
- 4. •Targeting of drugs also help us to bypass first pass metabolism so a drug can be administered in a form such that it reaches the receptor sites in sufficient concentration without disturbing in extraneous tissue cells. •Targeted drug delivery system should be- biochemically inert (non- toxic), non- immunogenic. •Both physically and chemically stable in vivo and in vitro. •Restrict drug distribution to target cells or tissues or organs and should have uniform capillary distribution. •Controllable and predictable rate of drug release. •Should have therapeutic amount of drug release. •Should have minimal drug leakage during transit. •Carriers used should be bio-degradable or readily eliminated from the body without any problem. •The preparation of the delivery system should be easy or reasonably simple, reproductive and cost effective. CHARACTERISTICS
- 5. ADVANTAGES DIS ADVANTAGES • Rapid clearance of targeted systems. • Immune reactions against intravenous administered carrier systems. • Insufficient localization of targeted systems into tumour cells. • Diffusion and redistribution of released drugs. • Drug administration protocols may be simplified. • Drug quantity may be greatly reduced as well as the cost of therapy. • Drug concentration in the required sites can be sharply increased without negative effects on non-target compartments.
- 6. 1)Passive Targeting 2)Active Targeting 3)Inverse Targeting 4)Ligand Mediated Targeting 5)Physical Targeting 6)Dual Targeting 7)Double Targeting STRATEGIES OF DRUG TARGETING
- 7. 1) Passive Targeting :- •Drug delivery systems which are targeted to systemic circulation are characterized as Passive delivery systems. •In this technique drug targeting occurs because of the body’s natural response to physicochemical characteristics of the drug or drug carrier system. 2) Active Targeting:- In this approach carrier system bearing drug reaches to specific site on the basis of modification made on its surface rather than natural uptake by RES. • Surface modification technique include coating of surface with either a bioadhesive, nonionic surfactant or specific cell or tissue antibodies (i.e. monoclonal antibodies) or by albumin protein. There are 3 Types of Active Targeting 1. First order targeting (organ compartmentalization). 2. Second order targeting (cellular targeting). 3. Third order targeting (intracellular targeting). STRATEGIES OF DRUG TARGETING
- 8. STRATEGIES OF DRUG TARGETING 3) Inverse Targeting :- •In this type of targeting attempts are made to avoid passive uptake of colloidal carrier by RES (Reticulo Endothelial Systems) and hence the process is referred to as inverse targeting. •To achieve inverse targeting, RES normal function is suppressed by pre injecting large amount of blank colloidal carriers or macromolecules like dextran sulphate •This approach leads to saturation of RES and suppression of defence mechanism. •This type of targeting is a effective approach to target drug(s) to non-RES organs. 4)Ligand Mediated Targeting :- Achieved using specific mechanisms such as receptor dependent uptake of natural LDL particles and synthetic lipid microemulsions of partially reconstituted LDL particles coated with the apoproteins.
- 9. STRATEGIES OF DRUG TARGETING 5)Physical Targeting :- •In this type of targeting some characteristics of environment changes like pH, temperature, light intensity, electric field, ionic strength small and even specific stimuli like glucose concentration are used to localize the drug carrier to predetermined site. •This approach was found exceptional for tumour targeting as well as cytosolic delivery of entrapped drug or genetic material. 6) Dual Targeting :- •In this targeting approach carrier molecule itself have their own therapeutic activity and thus increasethe therapeutic effect of drug. •For example, a carrier molecule having its own antiviral activity can be loaded with antiviral drug and the net synergistic effect of drug conjugate was observed. 7) Double Targeting :- •Temporal and spatial methodologies are combined to target a carrier system, then targeting may be called double targeting. •Spatial placement relates to targeting drugs to specific organs, tissues, cells or even subcellular compartment. whereas temporal delivery refers to controlling the rate of drug delivery to target site.
- 10. •Targeted drug delivery can be achieved by using carrier system. •Carrier is one of the special molecule or system essentially required for effective transportation of loaded drug up to the pre selected sites. •They are engineered vectors, which retain drug inside or onto them either via encapsulation and/ or via spacermoiety and transport or deliver it into vicinity of target cell. Pharmaceutical carriers : Polymers Microcapsules Microparticles Lipoproteins Liposomes Micelles Nanoparticles CARRIER OR MARKERS
- 11. NANOPARTICLES
- 12. INTRODUCTION The prefix nano comes from the ancient Greek vavoc through the Latin nanus meaning very small. Nanoparticles are defined as particulate dispersions or solid particles with a size in the range of 10-1000nm. The drug dissolved, entrapped, encapsulated or attached to a nanoparticle matrix. The term nanoparticle is a combined name for both nanospheres and nanocapsules. Drug is confined to a cavity surrounded by a unique polymer membrane called nanocapsules, while nanospheres are matrix systems in which the drug is physically and uniformly dispersed.
- 13. NANOPARTICLES NANOCAPSULES- The nanocapsules are system in which the drug is confined to a cavity surrounded by a unique polymer membrane. NANOSPHERES- The nanospheres are matrix systems in which the drug is physically and uniformly dispersed.
- 14. IDEAL PROPERTIES OF NANOPARTICLES NECESSARY FOR DRUG DELIVERY Stable in blood Nontoxic Non-thrombogenic Non- inflammatory Non-immunogenic Biodegradable
- 15. ADVANTAGES OF NANOPARTICLES Fairly easy preparation Good protection of the encapsulated drug Increased therapeutic efficacy Targeted and drug delivery Retention of drug at the active site Increased bioavailability Good control over size and size distribution Longer clearance time Dose proportionality
- 16. ADVANTAGES OF NANOPARTICLES • Nanoparticles have many significant advantage over conventional and traditional drug delivery system. • Nanoparticles are control and sustain release form at the site of localization, they alter organ distribution of drug compound. They enhance drug circulation in blood, bioavailability, therapeutic efficacy and reduce side effects. • Nanoparticles can be administer by various routes including oral, nasal, parenteral, intra-ocular etc. • In the tiny areas of body nanoparticles shows better drug delivery as compare to other dosage form and target to a particular cell type or receptor. • Nanoparticle enhance the aqueous solubility of poorly soluble drug, which improves bioavailability of drug. • As a targeted drug carrier nanoparticles reduce drug toxicity and enhance efficient drug distribution. • Useful to diagnose various diseases. • Enhanced stability of ingredients.
- 17. DISADVANTAGES OF NANOPARTICLES Limited targeting abilities Discontinuation of therapy is not possible Toxicity Disturbance of Autonomic imbalance Cytotoxicity
- 18. NANOMEDICINES FOR DRUG DELIVERY
- 19. S.NO TYPES OF NANOPARTICLE MATERIALS UED APPLICATION 1 Nanosuspensions and Nanocrystals Drug powder is disperse d in surfactant solution Stable system for controlled delivery of poorly soluble drug 2 Solid lipid Nanoparticles Melted lipid dispersed in Aqueous surfactant Least toxic and more stable Colloidal carrier systems as alternative materials To polymers 3 Polymeric nanoparticles Biodegradable polymer Controlled and targeted drug delivery 4 Polymeric micelles Amphiphilic block co polymers Controlled and systemic Delivery of water insoluble Drugs 5 Magnetic Nanoparticles Magnetite Fe2O3,Meghe Mite coated with dextran Drug targeting diagnostics to in medicine 6 Carbon Nanotubes Metals ,semiconductors Gene and DNA delivery
- 20. ROUTES
- 21. POLYMER USED IN PREPARTION Natural Hydrophilic PROTEINS POL YSACCHARIDES Synthetic Hydrophobic PRE- POLYMERIZED POLYMERIZED IN PROCESS
- 22. NATURAL HYDROPHILIC POLYMER PROTEINS POLYSACCHARIDES Gelatin Alginates Albumin Dextran Lectins Chitosan Legumin Agarose Vicilin Pullulan
- 23. SYNTHETIC HYDROPHOBIC POLYMER PRE-POLYMERIZED POLYMERIZED IN PROCESS Poly (e-caprolactone) (PECL) Poly(isobutylcyanoacrylates) (PICA) Poly(lactic acid) (PLA) Poly(butylcyanoacrylates) (PBCA) Poly(actide -co- glycolide (PLGA) Polyhexylcyanoacrylate (PHCA) Polystyrene Poly methyl (methacrylate)(PMMA)
- 25. METHODS OF PREPARATION OF NANOPARTICLES BY DISPERSION OF PREFORMED POLYMER
- 26. METHOD FOR PREPARATION OF NANOPRATICLES BY POLYMERIZATION OF MONOMERS EMULSION POLYMERIZA TION MINI- EMULSION POLYMRIZA TION MICRO-EMULSION POLYMRIZATION INTERFACIACL POLYMERIZA TION CONTROLLED/ LIVING RADICAL POLYMERIZATION
- 28. PREPARATION TECHNIQUES Solvent Evaporation:- • Solvent evaporation method first developed for preparation of nanoparticles. • In this method firstly nanoemulsion formulation prepared. • Polymer dissolved in organic solvent (dichloromethane, chloroform or ethyl acetate). • Drug is dispersed in this solution. • Then this mixuture emulsified in an aqueous phase containing surfactant (polysorbates, poloxamers, polyvinyl alcohol,). • This make an oil in water emulsion by using mechanical stirring, sonication, or micro fluidization (high-pressure homogenization through narrow channels).
- 29. Representation of the solvent – evaporation technique.
- 30. Double Emulsification Method:- •Emulsification and evaporation method have limitation of poor entrapment OF hydrophilic drugs, hence double emulsification technique is used. •Firstly w/o emulsion prepared by addition of aqueous drug solution to organic polymer solution with continuous stirring. •This prepared emulsion another aqueous phase with vigorous stirring, resultant w/o/w emulsion prepared, then organic solvent removed by high centrifugation. PREPARATION TECHNIQUES
- 31. Emulsions - Diffusion Method:- • This method patent by Leroux et al and it is modified form of salting out method. • Polymer dissolved in water-miscible solvent (propylene carbonate, benzyl alcohol), this solution saturated with water. • Polymer-water saturated solvent phase is emulsified in an aqueous solution containing stabilizer. Then solvent removed by evaporation or filtration. PREPARATION TECHNIQUES
- 32. Nano precipitation method:- • In this method precipitation of polymer and drug obtained from organic solvent and the organic solvent diffused in to the aqueous medium with or without presence of surfactant. • Firstly drug was dissolved in water, and then cosolvent (acetone used for make inner phase more homogeneous) was added into this solution. • Then another solution of polymer (ethyl cellulose, eudragit) and propylene glycol with chloroform prepared, and this solution was dispersed to the drug solution. • This dispersion was slowly added to 10 ml of 70% aqueous ethanol solution. PREPARATION TECHNIQUES
- 33. • After 5 minutes of mixing, the organic solvents were removed by evaporation at 35°under normal pressure, nanoparticles were separated by using cooling centrifuge (10000 rpm for 20 min), supernatant were removed and nanoparticles washed with water and dried at room temperature in a desicator. PREPARATION TECHNIQUES
- 34. Coacervation method:- • Drug and protein solution (2% w/v) incubated for one hour at room temperature and pH adjusted to 5.5 by using 1M HCl. • In this solution ethanol was added in 2:1 ratio (v/v) in a controle rate 1ml/min. • Resultant coacervate hardened with 25% glutaraldehyde (1.56 μg/mg of protein) for 2 hours which allow cross-linking of protein. • Rotary Vacuum evaporation at reduced pressure organic solvents were removed then nanoparticle were collected and purified by centrifugation at four degree centigrade. • Pellets of nanoparticles were then suspended in phosphate buffer (pH 7.4; 0.1 M) and lyophilized with mannitol. PREPARATION TECHNIQUES
- 35. Salting Out Method:- • Salting out method is very close to solvent diffusion method. • This technique is based on the separation of water- miscible solvent from aqueous solution by salting out effect. • In this method toxic solvents are not used. • Generally acetone is used because it is totally miscible with water and easily removed. PREPARATION TECHNIQUES
- 36. • Polymer and drug dissolved in a solvent which emulsified into a aqueous solution containing salting out agent (electrolytes, such as magnesium chloride and calcium chloride, or nonelectrolytes such as sucrose). PREPARATION TECHNIQUES
- 37. DIALYSIS:- Dialysis is an effective method for preparation of nanoparticles. In this method firstly polymer (such as Poly (benzyl-glutamate)-b- poly(ethylene oxide), Poly(lactide) and drug dissolved in a organic solvent. This solution added to a dialysis tube and dialysis performed. PREPARATION TECHNIQUES
- 38. EVALUATION PARAMETER OF NANOPARTICLES 1) YIELD OF NANOPARTICLES:- PrecentageYield = Amount of particle (100) Amount of drug+ polymer 2) DRUG CONTENT/SURFACE ENTRAPMENT/ DRUG ENTRAPMENT:- Precentage drug entrapment = W-w (100) W 3) PARTICLE SIZE:- Particle size and its distribution is important characteristics in nanoparticles as they plays major role in distribution, pharmacological activity, toxicity and targeting to specific sites. Advanced methods to determine the particle size of nanoparticles is by photon-correlation spectroscopy or dynamic light scattering, scanning electron microscopy
- 39. 4) PARTICLE SHAPE:- Particle shape of the nano suspensions is determined by scanning electron microscopy (SEM). In order to form the solid particles these nano suspensions were subjected to lyophilisation. 5) ZETA POTENTIAL:- Zeta potential is the potential difference existing between the surface of a solid particle immersed in a conducting liquid and the bulk of the liquid. The surface charge of the nanoparticles is usually measured by zeta potential. 4) DIFFERENTIAL SCANNING CALORIMERTY (DSC):- It is used to determine the nature of crystallinity within nanoparticles through the measurement of glass and melting point tempertures and their associated enthalpies. 5) ATOMIC FORCE MICROSCOPY (AFM):- It offers a ultra- high resolution in particle size measurement and is based on a physical scanning of sample at sub- micron level using a probe tip of atomic scale. AFM provides the most accurate description of size and size distribution and requires nom mathemical treatment.
- 40. DRUG LOADING INCORPORATION METHOD INCUBATION METHOD INCORPORATION METHOD- Incorporating at the time of nanoparticle production INCUBATION METHOD- Adsorbing the drug after the formation of nanoparticles by incubating the carrier with the concentrated drug solution. Both methods result in: Asolid solution of the drug in the polymers Solid dispersion of the dug in the polymer. Surface adsorption of the drug. Chemical bonding of the drug in the polymer.
- 41. DRUG RELEASE AND RELEASE KINETIC The release of drug from the particulate system depends upon three different mechanism: Release from the surface of particles. Diffusion through the swollen rubbery matrix. Release due to erosion.
- 42. EVALUATION FOR RELEASE OF DRUG Various methods which can be used to study the in vitro release of the drug from nanoparticles are: 1. Side-by- side diffusion cells with artifical or biological membranes 2. Dialysis bag diffusion technique 3. Reverse dialysis bag technique 4. Agitation followed by ultracentrifugation/ centrifugation 5. Ultra- filtration or centrifugal ultra- filtration techniques
- 43. IN VITRO DRUG RELEASE STUDIES USPType 2 RPM 50 Immersed in 900 ml of phosphate buffer solution Temperature 37+ 0.02 degree Celsius Withdrawn 5ml solution from the medium Specific time periods • DISSOLUTION:- Same vol. of dissolution medium replaced in the flask Maintain the constant volume Withdrawn samples analyzed using UV Spectrophotomete rer
- 44. • STABILITY OF NANOPARTICLES:- • Nanoparticles detemination • Storing optimized formulation 4 degree Celsius + 1 degree Celsius & 30 dergree celsius + 2 dergree celsius 0,1,2 & 3 month time period • Sample analyzed • Stability chamber for 90 days • Any changes in physical appearance Their drug content, drug release rate
- 45. APPLICATIONS USED IN TARGETED DRUG DELIVERYTO BRAIN THERAPY USED IN TARGETING OF NANOPRATICLES TO EPITHELIAL CELLS IN THE GI TRACT USING LIGANDS USED IN BIO DECTECTION OF PATHOGENS STEM CELL THERAPY NANOPARTICLES FOR GENE DELIVERY CANCER THERAPY
- 46. TYPES OF NANOPARTICLES Nanoparticles can be classified into different types according to the size, morphology, physical and chemical properties. Some of them are; 1.Carbon-based nanoparticles 2.Ceramic nanoparticles 3. Metal nanoparticles 4. Semiconductor nanoparticles 5. Polymeric nanoparticles 6. Lipid-based nanoparticles
- 47. 1. Carbon-based nanoparticles: It includes two main materials: a. Carbon nanotubes (CNTs). b. Fullerenes. CNTs are nothing but graphene sheets rolled into a tube. These materials are mainly used for the structural reinforcement as they are 100 times. Where as; Fullerenes are the allotropes of carbon having a structure of hollow cage of sixty or more carbon atoms. The structure of C-60 is also called Buckminsterfullerene. 2. Ceramic Nanoparticles • Ceramic nanoparticles are inorganic solids made up of oxides, carbides, carbonates and phosphates. • These nanoparticles have high heat resistance and chemical inertness. • They have applications in photocatalysis, photodegradation of dyes, drug delivery, and imaging. 3. Metal Nanoparticles • Metal nanoparticles are prepared from metal precursors. • These nanoparticles can be synthesized by chemical, electrochemical, or photochemical methods. • These nanoparticles have applications in detection and imaging of biomolecules and in environmental and bioanalytical applications. TYPES OF NANOPARTICLES
- 48. TYPES OF NANOPARTICLES 4. Semiconductor Nanoparticles • Semiconductor nanoparticles have properties like those of metals and non-metals. • These particles have wide bandgaps, which on tuning shows different properties. • They are used in photocatalysis, electronics devices, photo-optics and water splitting applications. • Some examples are Gan,Gap,Inp etc.from group III. 5. Polymeric Nanoparticles • Polymeric nanoparticles are organic based nanoparticles. • Depending upon the method of preparation, these have structures shaped like nanocapsular or nanospheres. A nanosphere particle has a matrix-like structure whereas the nanocapsular particle has core-shell morphology. 6. Lipid-Based Nanoparticles • Lipid nanoparticles are generally spherical in shape with a diameter ranging from 10 to 100nm. • It consists of a solid core made of lipid and a matrix containing soluble lipophilic molecules. • The external core of these nanoparticles is stabilized by surfactants and emulsifiers.
- 49. Liposomes
- 50. Liposomes are concentric bilayered vesicles in which an aqueous core is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids. LIPOSOMES
- 51. •Liposomes are extensively used as carriers for numerous molecules in cosmetic and pharmaceutical industries. Additionally, food and farming industries have extensively studied the use of liposome encapsulation to grow delivery systems that can entrap unstable compounds (for example, antimicrobials, antioxidants, flavors and bioactive elements) and shield their functionality. •The size of a liposome ranges from some 20 nm up to several micrometers. LIPOSOMES
- 52. Basic structure of liposome •A Lamella is a flat plate like structure that appears during the formation of liposomes. •The phospholipids bilayer first exists as a lamella before getting converted into spheres. •Several lamella of phospholipids bilayers are stacked one on top of the other during formation of liposomes to form a multilamellar structure.
- 53. •Provides selective passive targeting to tumor tissues. •Increased efficacy and therapeutic index. •Increased stability of encapsulated drug. •Reduction in toxicity of the encapsulated agent. •Improved pharmacokinetic effects. •Site avoidance effect (avoids non-target tissues). Liposomes are non-toxic, flexible, biocompatible, completely biodegradable, and nonimmunogenic for systemic and non-systemic administrations. ADVANTAGES OF LIPOSOMES
- 54. •Physical/ chemical stability. •Very high production cost. •Drug leakage/ entrapment/ drug fusion. •Sterilization. •Short biological activity / t ½. •Oxidation of bilayer phospholipids. •Overcoming resistance. •Repeated iv administration problems. DISADVANTAGES
- 55. PREPARATION OF LIPOSOMES General methods of preparation All the methods of preparing the liposomes involve four basic stages: 1. Drying down lipids from organic solvent. 2. Dispersing the lipid in aqueous media. 3. Purifying the resultant liposome. 4. Analyzing the final product. Method of liposome preparation and drug loading The following methods are used for the preparation of liposome: 1. Passive loading techniques 2. Active loading technique.
- 56. PREPARATION OF LIPOSOMES Passive loading techniques include three different methods: 1. Mechanical dispersion method. 2. Solvent dispersion method. 3. Detergent removal method (removal of nonencapsulated material) 1. Mechanical dispersion method The following are types of mechanical dispersion methods: 1.1. Sonication. 1.2. French pressure cell: extrusion. 1.3. Freeze-thawed liposomes. 1.4. Lipid film hydration by hand shaking, non-hand. shaking or freeze drying. 1.5. Micro-emulsification. 1.6. Membrane extrusion. 1.7. Dried reconstituted vesicle.
- 57. PREPARATION OF LIPOSOMES 2. Solvent dispersion method:- This methods includes: 2.1Ethanol injection. 2.2Ether injection. 2.3Double emulsion vesicles. 2.4Stable plurilamellar. 2.5Vesicles. 2.6Reverse phase evaporation vesicles. 3. Detergent removal method (removal of nonencapsulated material):- This methods includes detergent(Cholate,Alkylglycoside,Triton X-100) removal from mixed micelles by: 3.1Dialysis. 3.2Column chromatography. 3.3Dilution. 3.4Reconstituted sendai virus enveloped vesicles.
- 58. Evaluation of liposomes Physical properties 1. Particle size: Both particle size and particle size distribution of liposomes influence their physical stability. These can be determined by the following method. A. Laser light scattering. B. Transmission electron microscopy. 2. Surface charge: This technique can be used for determining the heterogeneity of charges in the liposome suspension as well as to detect any impurities such as fatty acids. 1. The positive, negative or neutral charge on the surface of the liposomes is due to the composition of the head groups. 2. The surface charge of liposomes governs the kinetic and extent of distribution in vivo, as well as interaction with the target cells. 3. The method involved in the measurement of surface charge is based on free-flow electrophoresis of MLVs.
- 59. 3. Percent drug encapsulated • Quantity of drug entrapped in the liposomes helps to estimate the behavior of the drug in biological system. • Liposomes are mixture of encapsulated and unencapsulated drug fractions. • The % of drug encapsulation is done by first separating the free drug fraction from encapsulated drug fraction. 4. Phase behavior • At transition temperature liposomes undergo reversible phase transition. • The transition temperature is the indication of stability permeability and also indicates the region of drug entrapment. • Done by DSC. 5. Drug Release Rate • The rate of drug release from the liposomes can be determined by in vivo assays which helps to predict the pharmacokinetics and bioavailability of the drug. • However in vivo studies are found to be more complete. Evaluation of liposomes
- 60. Benefits of drug load in liposomes Sr.No. Benefits of drug load in liposome Examples 1. Improved solubility of lipophilic and amphiphilic drugs Amphotericin B, porphyrins, minoxidil, some peptides, and anthracyclines, respectively; hydrophilic drugs, such as anticancer agent doxorubicin or acyclovir 2. Passive targeting to the cells of the immune system, especially cells of the mononuclear phagocytic system Antimonials, amphotericin B, porphyrins, vaccines, immunomodulators 3. Sustained release system of systemically or locally administered liposomes Doxorubicin, cytosine arabinoside, cortisones, biological proteins or peptides such as vasopressin 4. Site-avoidance mechanism Doxorubicin andamphotericin B 5. Site-specific targeting Anti-inflammatory drugs, anti-cancer, anti- infection 6. Improved transfer of hydrophilic, charged molecules Antibiotics, chelators, plasmids, and genes 7. Improved penetration into tissues Corticosteroids, anesthetics, and insulin
- 61. • Liposomes as drug or protein delivery vehicles. • Liposome in antimicrobial, antifungal (lung therapeutics) and antiviral (anti HIV) therapy. • In tumor therapy. • In gene therapy. • In immunology. • Liposomes as artificial blood surrogates. APPLICATIONS