03_Spandana_LIPOSOMES_PPT

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LIPOSOMES:

LIPOSOMES NAME: V.SPANDANA REGISTRATION NUMBER: 133H1S1103 BRANCH: PHARMACEUTICAL TECHNOLOGY COLLEGE: SRI SAI ADITYA INSTITUTE OF PHARMACEUTICAL SCIENCES & RESEARCH

CONTENTS:

CONTENTS INTRODUCTION MECHANISM OF LIPOSOME FORMATION TYPES OF PHOSPHOLIPIDS CLASSIFICATION BIOLOGICAL FATE OF LIPOSOMES ADVANTAGES & DISADVANTAGES METHODS OF PREPARATION CHARACTERIZATION OF LIPOSOMES STABILITY OF LIPOSOMES LIPOSOMAL PHARMACOKINETICS APPLICATIONS

INTRODUCTION:

INTRODUCTION Liposomes were discovered by Bhangam and co-workers in 1960’s. Liposomes are simple microscopic , concentric bi-layered vesicles in which an aqueous volume is entirely enclosed by a membranous lipid bi-layer mainly composed of phospholipids and cholesterol. The exact location of the drug in the liposome depends up on the physicochemical characterization of the drug and the composition of the lipid content. Stable liposomes from phospholipids are formed only as temperature above the “gel to liquid crystalline” phase transition temperature (Tc)

LIPOSOME:

LIPOSOME

Mechanism of liposome formation:

Mechanism of liposome formation

PowerPoint Presentation:

Vesicles are formed by hydrophobic effect. Ratio of hydrophilic and hydrophobic moieties. Critical packing parameter (CPP) If CPP value is less than 0.5 then liposomes are formed by hydrophobic effect. If CPP value is more than 0.5 then liposomes are formed by hydrophilic effect. If CPP value is between 0.5 – 1 then liposomes are formed by surfactant effect. CPP = v / lc Ap = Ahp / Ap Where: v = hydrophobic group volume lc = hydrophobic group length AP = cross sectional area of hydrophilic head group Ahp = cross sectional area of hydrophobic head group

TYPES OF PHOSPHOLIPIDS USED IN LIPOSOMES :

TYPES OF PHOSPHOLIPIDS USED IN LIPOSOMES The phospholipids used in liposomes are Phosphotidyl choline Phosphotidyl ethanolamine Phosphotidyl serine Phosphotidyl glycerol Cholesterol alone cannot form liposome but with lipids it intercalates i.e., Hydroxyl group aligns towards water surface and aliphatic chain parallel to acyl chains in the center of bi-layer. Widely used polar phospholipids is phosphotidyl choline which is used alone and in combination with cholesterol. Cholesterol condenses the packing of phospholipids in bi-layer above the phase transition temperature

phospholipids:

phospholipids

classification:

classification BASED ON STRUCTURE : Multi-lamellar large vesicles (>0.5 µm) MLV Oligo-lamellar vesicles (0.1 – 1µm) OLV Uni-lamellar vesicles ( All size ranges) UV Small uni-lamellar vesicles (20 – 100 nm) SUV Medium size uni-lamellar vesicles (>100 nm) MUV Large uni-lamellar vesicles (>100 nm) LUV Giant uni-lamellar vesicles (>1 µm) GUV Multi-vesicular vesicles (>1 µm) MV BAESD ON LIPOSOMAL FORMATION: Reverse phase evaporation REV Multi-lamellar vesicle by REV MLV-REV Stable plurilamellar vesicle SPLV Frozen and thawed MLV FATLV Vesicles prepared by extrusion techniques VET Dried reconstituted vesicles DRV

BIOLOGICAL FATE OF LIPOSOMES:

BIOLOGICAL FATE OF LIPOSOMES Liposomes in blood stream taken up by reticulo- endothelial system. The macrophages engulf the liposomes which are taken by the reticulo-endothelial system (endocytosis). Then phagosome and lysosome combine and form as a phagolysosome. The membrane of phagolysosome have proton pumps which decrease the pH of phagolysosome and the enzyme phospholipase destruct the liposomal membrane and releases the drug from destructed liposome.

ADVANTAGES & DISADVANTAGES:

ADVANTAGES & DISADVANTAGES ADVANTAGES: Biocompatibility and Biodegradability. Easy manufacture. Targeted drug delivery Prolonged circulation in stealth mode Able to protect encapsulated drug from degradation. DISADVANTAGES: Poor stability High manufacturing cost Poor loading capacity Challenging sterilization Poor reproducibility

METHODS OF PREPARATION:

METHODS OF PREPARATION Liposomes are prepared by two methods. They are:- Passive Loading Technique Active Loading Technique PASSIVE LOADING TECHNIQUE: The passive loading technique again subdivided into 3 methods. Mechanical Dispersion Method Lipid Film Hydration Hand Shaking Non Hand Shaking Freeze Drying Microemulsion Sonication French Pressure cell Membrane Extrusion Dried reconstituted Vesicles Freeze Thawed Liposomes

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SOLVENT DISPERSION METHODS Ethanol injection Ether injection Double Emulsion Vesicles Reverse Phase Evaporation Stable Plurilamellar Vesicles DETERGENT REMOVAL METHODS Detergent ( cholate,alkyl glycoside) removal from micelles by dialysis Column Chromatography Dilution

CHARACTERIZATION OF LIPOSOMES:

CHARACTERIZATION OF LIPOSOMES Visual appearance Vesicle shape and lamellarity (No.of bi-layers): Sample + 31p NMR + Manganese ( affect signal intensity) If intensity is decreased by 50% it forms unilamellar vesicles. If intensity is decreased by more intensity Multilamellar vesicles are formed. Freeze fracture electron microscopy Optical microscopy Vesicle size Light microscopy Fluorescent microscopy Electron microscopy :SEM,TEM Laser light scattering Gel permeation Ultracentrifugation Optical microscopy

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Liposome stability : Determined by physical , biological and chemical methods. Surface charge : Determined by Electrophoresis(Zeta potential) Drug release : Dissolution Entrapped volume : (water content is determined) Water is replaced with deuterium oxide & is analyzed by NMR . Encapsulation efficiency : Protamine aggregation method : Liposome + protamine = precipitation Centrifuge(2000 rpm), remove supernatant Liposome pellet + Trixon x-100 (surface breaker) The encapsulation efficiency can be determined (Analytically) Mini column centrifugation Chemical characterization Quantitative determination of phospholipids Phospholipid hydrolysis Phospholipid oxidation Cholesterol analysis

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Phospholipid determination: (Bartlett assay) Phospholipid phosphorus + Hydrolysis = Inorganic phosphate Inorganic phosphate + ammonium molybdate = Phosphomolybdic acid Phosphomolybdic acid + Amino naphthyl sulfonic acid = reduced to blue color whose intensity is measured and compared with standard Phospholipid Hydrolysis: Phospholipids + Hydrolysis = Lysolecithin One chain is lost by deesterification Determined by HPLC Phospholipid oxidation: Free radical determination by UV, Iodometric method, GLC etc. Cholesterol analysis: Cholesterol + Iron + Reagent ( Ferric perchlorate, ethyl acetate sulfuric acid = purple complex , which is determined at 610 nm).

STABILITY OF LIPOSOMES:

STABILITY OF LIPOSOMES Liposomes stability can be done in two ways. In vitro stability In vivo stability IN VITRO STABILITY: Liposomes are not thermodynamically stable but they represents a metastable state. Liposomal vesicles possess excess energy. Phospholipids are prone to oxidation and hydrolysis leads to their degradation. The method of preparation, nature of amphipile and the encapsulated drug effects membrane fluidity/rigidity and permeability characteristics. Drug leakage from aqueous domains of lipid bilayers i.e., Hydrophilic drugs. Physicochemical and bio environmental stimuli.

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IN VIVO STABILITY: Rapid RES uptake fast biodegradation. Gastric stability for orally administered liposomes LIPOSOMAL PHAMACOKINETICS: Protection of drug from metabolism and inactivation in plasma. Decreased volume of distribution and hence decrease in non specific localization of drug. High therapeutic index. Decreased amount and type of non specific toxicity. Increase in concentration of drug at target site.

APPLICATIONS:

APPLICATIONS Formulation of antineoplastic drugs into liposomes will significantly enhances systemic circulation time. Decreased toxicity by reducing free drug levels in plasma. Increased EPR (Enhanced permeability &retention effect). Decreased cardio-toxicity of Doxorubicin by liposomal encapsulation. Positively charged liposomes have enhanced immunogenic properties for vaccines and hypersensitivity responses. PEGylated liposomes are recent advancement in brain targeted drug delivery systems. Liposomes used as drug carriers for efficient treatment of neuronal inflammation (Methyl prednisolone) & others exhibited superior anti inflammatory activity than

COMMERCIALLY AVAILABLE LIPOSOMES:

COMMERCIALLY AVAILABLE LIPOSOMES BRAND NAME DRUG CATEGORY ROUTE Doxil Doxorubicin Anticancer Intravenous Daunoxome Daunorubicin Anticancer Intravenous Epaxel Hepatitis A vaccine Protection against Hepatitis Subcutaneous Elamax Lidocaine Local anesthetic Topical Mikasome Amikacine Antibacterial Intravenous

DRUGS UNDER RESEARCH / INVESTIGATION:

DRUGS UNDER RESEARCH / INVESTIGATION DRUGS CATEGORY ROUTE OF ADMINISTRATION Oleonolic acid Anticancer Oral Midazolam Sedative Oral Diclofenac sodium Arthritis Topical Cytarabine Anticancer Parentral Insulin Diabetes Mellitus Pulmonary Acyclovir Genital Herpes Vaginal

CONCLUSION:

CONCLUSION Liposomes are extremely useful drug carrier systems , additives and tools in various scientific domains. Specially for drug delivery and targeting in pharmaceutical fields. The use of liposomes in delivery of drugs and genes to tumour sites are more promising and may serve as a major area for focus of future research.

REFERENCE:

REFERENCE www.slideshare.com www.authorstream.com Targetted & controlled Drug delivery Novel carrier systems - S.P.Vyas - R.K.Khar Novel drug delivery systems by N.K.Jain

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