liposomes

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Slide 1: 

PRESENTED BY SUNIL SHIMBRE M.PHARM- Ist YEAR. WEL COME TOSEMINARON LIPOSOMES

WHAT ARE LIPOSOMES? : 

WHAT ARE LIPOSOMES? Liposomes are simple microscopic vesicle in which an aqueous volume  is entirely  enclosed by a membrane composed of a lipid molecule. Structurally, liposomes are concentric bilayered vesicles in which an aqueous volume is entirely enclosed  by a membraneous lipid bilayer mainly composed of natural or synthetic phospholipids. 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 2 Hydrophilic Hydrophobic

LETS TAKE A LOOK AT A LIPOSOME : 

LETS TAKE A LOOK AT A LIPOSOME 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 3 Hydrophobic Hydrophilic cavity

Why Use Liposomes in Drug Delivery? : 

Why Use Liposomes in Drug Delivery? Drug Targeting Inactive: Unmodified liposomes gather in specific tissue reticuloendothelial system Active: alter liposome surface with ligand (antibodies, enzymes, protein A, sugars). Physical: temperature or pH sensitive liposomes Directly to site 07/12/2009 4 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE

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Pharmacokinetics - efficacy and toxicity Changes the absorption and biodistribution Deliver drug in desired form Protection Decrease harmful side effects Protects drug 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 5

ADVANTAGES OF LIPOSOMES : 

ADVANTAGES OF LIPOSOMES Provides selective passive targeting to tumor tissues  (liposomal doxorubicin) (in short tissue targetting). Increased efficacy and therapeutic index Reduction in toxicity of the encapsulated agent Site avoidance effect (avoids non-target tissues) Improved pharmacokinetic effects (reduced  elimination increased circulation life times) Flexibility to couple with site-specific ligands to achieve  active targeting. 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 6

STRUCTURAL COMPONENTS OF LIPOSOMES : 

STRUCTURAL COMPONENTS OF LIPOSOMES THE MAIN COMPONENTS OF LIPOSOMES ARE:- PHOSPHOLIPIDS CHOLESTEROL 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 7

PHOSPHOLIPIDS : 

PHOSPHOLIPIDS Phospholipids are the major structural components of biological membranes such as  the cell membrane. 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 8 TWO TYPES OF  PHOSPHOLIPIDS (ALONG WITH THEIR HYDROLYSIS PRODUCTS) PHOSPHOGLYCERIDES SPHINGOLIPIDS

Phosphatidylcholine : 

Phosphatidylcholine Most common phospholipid 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 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 9

Generally phospholipids are represented as follows: : 

Generally phospholipids are represented as follows: 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 10

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Molecules of PC are not soluble in water. In aqueous media they align themselves closely in  planar bilayer sheets in order to minimize the  unfavorable action between the bulk aqueous  phase and the long hydrocarbon fatty chain.  • Such unfavorable interactions are completely   eliminated when the sheets fold on themselves to  form closed sealed vesicles 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 11

In short this is what happens : 

In short this is what happens 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 12

SOME OTHER COMMONLY USED PHOSPHOLIPIDS : 

SOME OTHER COMMONLY USED PHOSPHOLIPIDS Naturally occurring phospholipids: -PC : Phosphatidylcholine – PE : Phosphatidylethanolamine – PS : Phosphatidylserine Synthetic phospholipids: -DOPC : Dioleoylphosphatidylcholine – DSPC : Distearoylphosphatidylcholine 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 13

CHOLESTEROL : 

CHOLESTEROL Incorporation of sterols in liposome bilayer  brings  about major changes in the preparation of these  membranes. Cholesterol by it self does not form a bilayer structure. However, cholesterol acts as a fluidity buffer, i.e. below  the phase transition temperature, it makes the  membrane less ordered and slightly more permeable; while above the phase transition temperature it makes  the membrane more ordered and stable. 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 14

Cholesterol inserts into the membrane with its hydroxyl groups oriented towards the aqueous surface and aliphatic chain aligned parallel to the acyl chains in the center of the bilayer. : 

Cholesterol inserts into the membrane with its hydroxyl groups oriented towards the aqueous surface and aliphatic chain aligned parallel to the acyl chains in the center of the bilayer. 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 15

TYPES OF LIPOSOMES : 

TYPES OF LIPOSOMES Liposomes are classified on the basis of  – Structural parameters – Method of preparation – Composition and applications 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 16

What is a lamella? : 

What is a lamella? – A Lamella is a flat plate like structure that appearsduring the formation of liposomes. The phospholipidbilayer first exists as a lamella before getting converted into spheres.– Several lamella of phospholipid bilayers are stacked one on top of the other during formation of liposomes  to form a multilamellar structure. 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 17

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07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 18 Multilamellar vesicles Unilamellar vesicles

Based on structural parameters : 

Based on structural parameters 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 19 Based on structural  parameters MLV Multilamellar Large vesicles (>0.5 um) OLV oligolamellar vesicles (>0.1-1.0 um) UV UnilamellarVesicles (all size ranges) MVV Multivesicularvesicles (> 1.0 UM) MUV GUV >1um SUV 20-100nm LUV >100nm

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07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 20

Methods of liposome preparation : 

Methods of liposome preparation Passive loading techniques Active loading techniques 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 21

Passive loading techniques : 

Passive loading techniques Mechanical dispersion methods Solvent dispersion methods 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 22

mechanical dispersion method : 

mechanical dispersion method Hand-shaken multilamellar vesicles Non-shaking vesicles Pro- liposomes Freeze drying 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 23

Hand shaken method in general : 

Hand shaken method in general 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 24

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Non-shaking vesicles Pro- liposomes Freeze drying 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 25

Solvent dispersion methods : 

Solvent dispersion methods Ethanol injection method. Ether injection method. Reverse phase evaporation vesicles method. 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 26

Ethanol/Ether injection method : 

Ethanol/Ether injection method 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 27

Reverse phase evaporation vesicles : 

Reverse phase evaporation vesicles 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 28 partial  bilayer

REFERENCES:- : 

REFERENCES:- Target & Controlled Drug Delivery  Novel  Carrier Systems by S. P. Vyas & R. K. Khar Liposomes as drug carriers by  Sanjay K Jain and N K Jain 07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 29

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07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 30 Any Questions or Suggestions?

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07/12/2009 SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 31

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