Liposomes ppt

gurudayal yadav

1. Liposomes Gurudayal Yadav

2. Ou tli ne 3/25/2019 2

3. 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. The size of a liposome ranges from some 20 nm up to several micrometers. Liposomes 3/25/2019 3 L i p oso m e

4. The lipid molecules are usually phospholipids- amphipathic moieties with a hydrophilic head group and two hydrophobic tails . On addition of excess water, such lipid moieties spontaneously originate to give the most thermodynamically stable conformation. In which polar head groups face outwards into the aqueous medium, and the lipid chains turns inwards to avoid the water phase, giving rise to double layer or bilayer lamellar structures. 3/25/2019 4

5. Basic liposome structure 3/25/2019 5

6. La m e ll a 3/25/2019 6

7. Structural Components of Liposomes 3/25/2019 7

8. Phospholipids 3/25/2019 8 Phospholipids are the major structural components of biological membranes such as the cell membrane.

9. Phosphatidylcholine 3/25/2019 9 • Most common phospholipids used is phosphatidylcholine (PC). Phosphatidylcholine is an amphipathic molecule in which exists:- a hydrophilic polar head group, phosphocholine. a glycerol bridge. a pair of hydrophobic acyl hydrocarbon chains.

10. Generally phospholipids are represented as follows 3/25/2019 10

11. Cholesterol 3/25/2019 11

12. Advantages of liposomes 3/25/2019 12

13. Disadvantages Of liposomes 3/25/2019 13

14. Liposomes Evolution 1965 First description of closed lipid bilayer vesicles. 1967 introduction of the term liposomes to describe closed lipid bilayer vesicles 1972 liposomes first used as delivery systems of drugs 1974 first patients to be injected with liposomes 1979 liposomes first used as delivery systems of nucleic acids to cells 1980 first monoclonal anti body targeted liposomes termed immuno liposomes 1987 first synthetic cationic liposomes deliver genes to cells 1987 first sterically stabilized long circulating liposomes system introduced 3/25/2019 14

15. 1992 first liposome based non viral vector gene therapy clinical trail on cystic fibrosis patients. 1993 first liposome based vaccine against hepatitis A is marketed. 1995 first long circulating immune liposomes. 1995 the liposomes encapsulated from of the anticancer drug doxorubicin and daunorubicin approved for human use. 1997 first liposomes based DNA vaccine. 3/25/2019 15

16. Classification On the basis of structural parameters Multilamellar vesicles (> 0.5 µm ) MLV Oligo lamellar vesicles ( 0.1-1 µm ) OLV Unilamellar vesicles ( all size range) UV Small Unilamellar vesicles ( 20-100 nm) SUV Medium sized Unilamellar vesicles MUV Large Unilamellar vesicles (> 100 µm ) LUV Giant Unilamellar vesicles (> 1 µm ) GUV Multi vesicular vesicles (> 1 µm ) MVV On the basis of liposome preparation: Vesicles prepared by reverse phase evaporation method REV Multi lamellar vesicle by REV MLV-REV Stable plurilamellar vesicle SPLV Frozen & thawed MLV FATMLV Vesicles prepared by extrusion techniques VET Dried reconstituted vesicles DRV 12 3/25/2019 16

17. Method of liposome preparation Physical dispersion method : 1 . Hand shaking MLVs 2 . Non-shaking LUVs 3 . Freeze drying 4 . Pro-liposomes To reduce liposome size: 1 . Micro emulsification 2 . Membrane extrusion 3 . Ultrasonication 4 . French pressure cell To increase liposome size : 1 . Dried reconstituted vesicle 2 . Freeze thawing 3 . Induction of vesiculation by PH change 3/25/2019 17

18. Solvent dispersion method- Ethanol injection Ether injection Water organic phase: A ) Double emulsion method B ) Reverse phase evaporation C ) Stable plurilamellar vesicles. Detergent solubilization 3/25/2019 18

19. Physical dispersion method 3/25/2019 19

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23. To reduce liposome size- 3/25/2019 23

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30. Evaluation of l iposomes 3/25/2019 30 The liposomes prepared by various techniques are to be evaluated for their physical properties, has these influence the behavior of liposomes in vivo . Particle size and particle size distribution- Both particle size and particle size distribution of liposomes influence their physical stability. These can be determined by the following method. Laser light scattering Transmission electron microscopy

31. 3/25/2019 31 2. Surface charge The positive, negative or neutral charge on the surface of the liposomes is due to the composition of the head groups. T he surface charge of liposomes governs the kinetic and extent of distribution in vivo, as well as interaction with the target cells. The method involved in the measurement of surface charge is based on free-flow electrophoresis of MLVs. It utilizes a cellulose acetate plate dipped in sodium borate buffer of pH 8.8. About 5 N moles o f lipid samples are applied on to m the plate , which is then subjected to electrophoresis at 4 ͦ c for 30 mins. The liposomes get bifurcated depending on their 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.

32. 3. Percent drug encapsulated. 3/25/2019 32 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 The encapsulated fraction is then made to leak off the liposome into aqueous solution using suitable detergents The methods used to separate the free drug from the sample are : Mini column centrifugation method Protamine aggregated method

33. 4. Phase behavior At transition temperature liposomes undergo reversible phase transition The t ran s i tion te m peratu r e is the indic a t ion of s t a b i lity 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. Liposome encapsulating the tracer [ᵌH] insulin are employed for the study. This [ᵌH] insulin is preferred, as it is released only in the ECF and undergoes rapid renal excretion of the face tracer coupled to the degradation rate constant o the tracer released from the liposomes 3/25/2019 33

34. Applications 3/25/2019 34

35. CONCLUSION Liposomes have been used in a broad range of pharmaceutical applications. Liposomes are showing particular promise as intracellular delivery systems for anti-sense molecules, ribosomes, proteins/peptides, and DNA. Liposomes with enhanced drug delivery to disease locations, by ability of long circulation residence times, are now achieving clinical acceptance. Also , liposomes promote targeting of particular diseased cells within the disease site. Finally , liposomal drugs exhibit reduced toxicities and retain enhanced efficacy compared with free complements. Only time will tell which of the above applications and speculations will prove to be successful. However , based on the pharmaceutical applications and available products, we can say that liposomes have definitely established their position in modern delivery systems. 3/25/2019 35

36. References Sahoo SK, Labhasetwar V. Nanotech approaches to drug delivery and imaging. DDT. 2003;8:24.[ PubMed ] Gabizon A, Goren D, Cohen R, Barenholz Y. Development of liposomal anthracyclines: from basics to clinical applications. J Control Release. 1998;53:275–279. doi : 10.1016/S0168-3659(97)00261-7.[ PubMed ] [ CrossRef ] Allen TM. Liposomes. Opportunities in drug delivery. Drugs. 1997;54( Suppl 4):8–14. [ PubMed ] Chrai SS, Murari R, Imran A. Liposomes: a review. Bio Pharm. 2001;14(11):10–14. Andreas W, Karola VU. Liposome technology for industrial purposes. J Drug Deliv . 2011;2011:9. Atrooz OM. Effects of alkylresorcinolic lipids obtained from acetonic extract of Jordanian wheat grains on liposome properties.  Int J Biol Chem. 2011;5(5):314–321. 3/25/2019 36

37. 3/25/2019 37 THANK YOU…