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Dr. Subhash V. Deshmane
Associate Professor
Rajarshi Shahu College of Pharmacy
Buldana. M.S. India
www.rscp.ac.in
Email: subdeshmane@yahoo.co.in
WHATARE 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 bil
ayered vesicles in which an aqueous
volume is entirely
enclosed by a membraneous
lipid bilayer mainly composed of natural
or synthetic phospholipids.
2
Hydrophilic
Hydrophobic
LETS TAKE A LOOK AT A LIPOSOME
3
Hydrophobic
Hydrophilic
cavity
Why Use Liposomes in Drug Delivery?
 DrugTargeting
 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
 Pharmacokinetics - efficacy and toxicity
 Changes the absorption and
biodistribution
 Deliver drug in desired form
 Protection
 Decrease harmful side effects
 Protects drug
5
ADVANTAGESOFLIPOSOMES
 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.
6
STRUCTURAL COMPONENTS OF LIPOSOMES
 THE MAIN COMPONENTS OF LIPOSOMESARE:-
 PHOSPHOLIPIDS
 CHOLESTEROL
7
PHOSPHOLIPIDS
Phospholipids are the major structural components of
biological membranes such as the cell membrane.
8
TWO TYPES OF
PHOSPHOLIPIDS (ALONG
WITH THEIR
HYDROLYSIS PRODUCTS)
PHOSPHOGLYCERIDES
SPHINGOLIPIDS
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
9
Generally phospholipids are represented as
follows:
10
 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
11
In short this is what happens
07/12/2009SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 12
SOME OTHER COMMONLY USED
PHOSPHOLIPIDS
 Naturally occurring phospholipids:
-PC : Phosphatidylcholine
– PE : Phosphatidylethanolamine
– PS : Phosphatidylserine
 Synthetic phospholipids:
-DOPC : Dioleoylphosphatidylcholine
 – DSPC : Distearoylphosphatidylcholine
13
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.
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.
15
TYPES OF LIPOSOMES
 Liposomes are classified on the basis of
– Structural parameters
– Method of preparation
– Composition and applications
16
What is a lamella?
– A Lamella is a flat plate like structure that appears during
the formation of liposomes.The phospholipid bilayer 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 multila
mellar structure.
17
18
Multilamellar vesiclesUnilamellar vesicles
Based on structural parameters
19
Based on structural
Based on structural
parameters
MLV
Multilamellar
Large
vesicles
(>0.5 um)
OLV
oligolamellar
vesicles
(>0.1-1.0 um)
UV Unilamellar
Vesicles (all siz
e ranges)
MVV
Multivesicular
vesicles
(> 1.0 UM)
MUV
GUV
>1um
SUV
20-
100nm
LUV
>100nm
Based on
method of
preparation
REV, SUV made by
reverse phase
evaporation
method
SPLV
Stable
plurilamenar
vesicles
FATMLV
Frozen
&thawed MLV
VET
Vesicles
prepared by
extrusion
tech.
20
Methods of liposome preparation
 Passive loading techniques
 Active loading techniques
21
Passive loading techniques
 Mechanical dispersion methods
 Solvent dispersion methods
22
mechanical dispersion method
 Hand-shaken multilamellar vesicles
 Non-shaking vesicles
 Pro- liposomes
 Freeze drying
23
Hand shaken method in
general
24
 Non-shaking vesicles
 Pro- liposomes
 Freeze drying
25
Solvent dispersion methods
 Ethanol injection method.
 Ether injection method.
 Reverse phase evaporation vesicles method.
26
Ethanol/Ether injection method
27
Reverse phase evaporation vesicles
28
At this stage-
the monolayers come
close to each other
In rotar y evaporator close to each other
partial bilayer
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
29
07/12/2009SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 30

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Liposomes by Dr. S. V. Deshmane

  • 1. Dr. Subhash V. Deshmane Associate Professor Rajarshi Shahu College of Pharmacy Buldana. M.S. India www.rscp.ac.in Email: subdeshmane@yahoo.co.in
  • 2. WHATARE 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 bil ayered vesicles in which an aqueous volume is entirely enclosed by a membraneous lipid bilayer mainly composed of natural or synthetic phospholipids. 2 Hydrophilic Hydrophobic
  • 3. LETS TAKE A LOOK AT A LIPOSOME 3 Hydrophobic Hydrophilic cavity
  • 4. Why Use Liposomes in Drug Delivery?  DrugTargeting  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
  • 5.  Pharmacokinetics - efficacy and toxicity  Changes the absorption and biodistribution  Deliver drug in desired form  Protection  Decrease harmful side effects  Protects drug 5
  • 6. ADVANTAGESOFLIPOSOMES  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. 6
  • 7. STRUCTURAL COMPONENTS OF LIPOSOMES  THE MAIN COMPONENTS OF LIPOSOMESARE:-  PHOSPHOLIPIDS  CHOLESTEROL 7
  • 8. PHOSPHOLIPIDS Phospholipids are the major structural components of biological membranes such as the cell membrane. 8 TWO TYPES OF PHOSPHOLIPIDS (ALONG WITH THEIR HYDROLYSIS PRODUCTS) PHOSPHOGLYCERIDES SPHINGOLIPIDS
  • 9. 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 9
  • 10. Generally phospholipids are represented as follows: 10
  • 11.  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 11
  • 12. In short this is what happens 07/12/2009SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 12
  • 13. SOME OTHER COMMONLY USED PHOSPHOLIPIDS  Naturally occurring phospholipids: -PC : Phosphatidylcholine – PE : Phosphatidylethanolamine – PS : Phosphatidylserine  Synthetic phospholipids: -DOPC : Dioleoylphosphatidylcholine  – DSPC : Distearoylphosphatidylcholine 13
  • 14. 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. 14
  • 15. 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. 15
  • 16. TYPES OF LIPOSOMES  Liposomes are classified on the basis of – Structural parameters – Method of preparation – Composition and applications 16
  • 17. What is a lamella? – A Lamella is a flat plate like structure that appears during the formation of liposomes.The phospholipid bilayer 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 multila mellar structure. 17
  • 19. Based on structural parameters 19 Based on structural Based on structural parameters MLV Multilamellar Large vesicles (>0.5 um) OLV oligolamellar vesicles (>0.1-1.0 um) UV Unilamellar Vesicles (all siz e ranges) MVV Multivesicular vesicles (> 1.0 UM) MUV GUV >1um SUV 20- 100nm LUV >100nm
  • 20. Based on method of preparation REV, SUV made by reverse phase evaporation method SPLV Stable plurilamenar vesicles FATMLV Frozen &thawed MLV VET Vesicles prepared by extrusion tech. 20
  • 21. Methods of liposome preparation  Passive loading techniques  Active loading techniques 21
  • 22. Passive loading techniques  Mechanical dispersion methods  Solvent dispersion methods 22
  • 23. mechanical dispersion method  Hand-shaken multilamellar vesicles  Non-shaking vesicles  Pro- liposomes  Freeze drying 23
  • 24. Hand shaken method in general 24
  • 25.  Non-shaking vesicles  Pro- liposomes  Freeze drying 25
  • 26. Solvent dispersion methods  Ethanol injection method.  Ether injection method.  Reverse phase evaporation vesicles method. 26
  • 28. Reverse phase evaporation vesicles 28 At this stage- the monolayers come close to each other In rotar y evaporator close to each other partial bilayer
  • 29. 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 29
  • 30. 07/12/2009SNIOP COLLEGE OF PHARMACY, PUSAD PRESENTED BY- S.R. SHIMBRE 30