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SEMINAR
MOLECULAR PHARMACEUTICS
LIPOSOMES- INTRODUCTION AND
TYPES
SUBMITTED BY,
ARDRA KRISHNA P V
MPHARM 2ND SEMESTER
DEPARTMENT OF PHARMACEUTICS
KMCH COLLEGE OF PHARMACY
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 1
CONTENT
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 2
INTRODUCTION
ADVANTAGES
DISADVANTAGES
TYPES
LIPOSOMES AND CANCER
MARKETED FORMULATIONS
TARGETING METHODS
• Rational Research in drug delivery
began in 1950s.
• Need for Targeted/controlled Drug
Delivery:
Delivery of the drug at a rate
and/or a location dictated by the
needs of the body or disease state
over a specified period of time.
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 3
LIPOSOMES
• Liposomes is Greek words means ‘Lipo’
mean ‘Fat’ and ‘Somes’ mean ‘Body’.
• 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 are extensively used as carriers
for numerous molecules in cosmetic and
pharmaceutical industries.
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 4
• Discovered in 1960‟s by Bangham and coworkers.
• The size range of liposome: 20 nm up to several micrometers.
• Due to their size and hydrophobic and hydrophilic character(besides
biocompatibility), liposomes are promising systems for drug delivery.
• The choice of bilayer components determines the ‘rigidity’ or ‘fluidity’
and the charge of the bilayer.
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 5
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 6
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 7
COMPOSITION OF LIPOSOMES
There are number of components of liposomes however Lecithin
(mixture of phospholipids) and cholesterol being main components.
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 8
PHOSPHOLIPIDS
Phospholipids are fatty substances the major structural components
of cell wall & biological membranes.
Phospholipids are amphipathic moieties with a hydrophilic head
group and two hydrophobic tails.
Two types of phospholipids exist – PHOSPHODIGLYCERIDES
AND SPHINGOLIPIDS, together with their corresponding
hydrolysis products.
• Phospholipids have phosphatidyl moiety (tail) with different head
groups (choline, Ethanolamine, Serine)
• The most common phospholipid is Phosphatidylcholine (PC)
molecule.
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 9
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 10
Phosphatidylcholine has
glycerol bridge links a
pair of hydrophobic acyl
hydrocarbon chains
having 10-24 carbon
atoms with a hydrophilic
polar head group.
ADVANTAGES
• Provides selective passive targeting to tumor tissues (liposomal
doxorubicin).
• Increased efficacy and therapeutic index.
• Increased stability via encapsulation.
• Reduction in toxicity of the encapsulated agent.
• Improved pharmacokinetic effects (reduced elimination, increased
circulation life times).
• Flexibility to couple with site-specific ligand to achieve active
targeting.
• Site avoidance effect (avoids non-target tissues).
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 11
DISADVANTAGES
• Very high production cost.
• Drug leakage/ entrapment/ drug fusion.
• Sterilization.
• Short biological activity / t ½.
• Oxidation of bilayer phospholipids.
• Repeated iv administration problems.
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 12
STERILIZATION OF LIPOSOMES
• Due to the particular sensitivity of liposomes and their tendency to
physicochemical alterations, their sterilization remains a real challenge.
Conventional sterilization methods such as heat, ethylene oxide, ultraviolet
and gamma irradiations are considered as unsuitable for liposome
sterilization.
• The search for an alternative method being therefore necessary, the
applicability of SUPERCRITICAL CARBON DIOXIDE (ScCO2)
TECHNOLOGY, which is nowadays a promising strategy for the
sterilization of sensitive products such as liposomes. ScCO2 could
effectively be an interesting alternative to achieve sterility of liposomes.
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 13
TYPES
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 14
BASED ON
METHOD OF
PREPARATION
BASED ON
STRUCTURAL
PARAMETERS
BASED ON
COMPOSITION
AND
APPLICATION
CLASSIFICATION
LIPOSOMES CAN BE CLASSIFIED BASED ON THREE DIFFERENT CRITERIA:
CLASSIFICATION OF LIPOSOMES
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 15
BASED ON
STRUCTURAL
PARAMETERS
MLV
Multilamellar
Vesicles (>0.5
μm)
OLV
Oligolamellar
Vesicles (0.1 – 1
μm)
UV Unilamellar
Vesicles (Full
size range)
SUV Small
Unilamellar
Vesicles (20 –
100 nm)
GUV Giant
Unilamellar
Vesicles ( >1
μm)
MUV Medium
Unilamellar
Vesicles
LUV Large
Unilamellar
Vesicles (>100
nm)
MVV / MV
Multivesicular
Vesicles (>1
μm)
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 16
BASED ON
COMPOSITION AND
APPLICATION
CL (
Conventional
liposomes)
Neutral/ Negatively charged
phospholipids and cholesterol
Fusogenic
Liposomes
RSVE – Reconstituted Sendai
Virus Envelop
pH sensitive
Liposomes
Using phospholipids such as PE or
DOPE with OA
Cationic
Liposomes
Cationic Lipids with DOPE
Long Circulatory (
stealth) Liposomes
( LCL)
High Tc made using cholesterol
and 5 – 10% PEG – DSPE or GM1
Immuno –
liposomes
With attached monoclonal
antibody
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 17
BASED ON
METHOD OF
PREPARATION
DRV
dehydrated
–
Rehydration
method
VET Vesicle
prepared by
extrusion
technology
REV SUVs/
OLVs made
by reverse –
phase
evaporation
method
FAT MLV
Frozen
and
Thawed
MLVs
MLV- REV
MLVs made
by reverse
phase
evaporation
method
SPLV
stable
plurilamell
ar Vesicles
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 18
NOVEL LIPOSOMES
TRANSFEROSOMES
ARCHEOSOMES
PROTEOSOMES
VIROSOMES
ETHOSOMES
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 19
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 20
TRANSFEROSOMES ARCHEOSOMES
VIROSOMES ETHOSOMES
MARKETED FORMULATIONS
CARRIER
SYSTEM
TARGETED SITE CARRIER FORMULATION MARKETED
EXAMPLES
IV TUMOR CELL LIPOSOMES POWDER , DISPERSION AND
SOLVENT FOR CONCENTRATE
FOR DISPERSION FOR INFUSION
myocet
IV FUNGAL CELL WALL LIPOSOMES POWDER FOR DISPERSION FOR
INFUSION AmBisome®
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 21
LIPOSOMES AND CANCER
• Liposomes have revolutionized
cancer therapy by their broad
clinical applications.
• Liposomes overcome the
limitations of conventional
chemotherapy by improving the
bioavailability and stability of the
drug molecules and minimizing
side effects by site-specific
targeted delivery of the drugs.
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 22
Biological Challenges Facing Liposomal
Drug Delivery Systems
As with any foreign particle that enters the body, liposomes
encounter multiple defense systems aimed at recognition, neutralization,
and elimination of invading substances. These defenses include the RES
(Reticuloendothelial system), opsonization, and immunogenicity. While
these obstacles must be circumvented for optimal liposome function,
other factors such as the enhanced permeability and retention (EPR)
effect can be exploited to enhance drug delivery.
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 23
REFERENCES
• Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S. et al. Liposome: classification,
preparation, and applications. Nanoscale Res Lett 8, 102 (2013).
https://doi.org/10.1186/1556-276X-8-102
• Sriram Vemuri, C.T Rhodes, Preparation and characterization of liposomes as
therapeutic delivery systems: a review, Pharmaceutica Acta Helvetiae, Volume 70,
Issue 2, 1995, https://doi.org/10.1016/0031-6865(95)00010-7
• Nina Filipczak, Jiayi Pan, Satya Siva Kishan Yalamarty, Vladimir P. Torchilin,
Recent advancements in liposome technology, Advanced Drug Delivery Reviews,
Volume 156, 2020, 4-22, https://doi.org/10.1016/j.addr.2020.06.022
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 24
THANK YOU!
12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 25

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LIPOSOMES INTRODUCTION AND TYPES.pptx

  • 1. SEMINAR MOLECULAR PHARMACEUTICS LIPOSOMES- INTRODUCTION AND TYPES SUBMITTED BY, ARDRA KRISHNA P V MPHARM 2ND SEMESTER DEPARTMENT OF PHARMACEUTICS KMCH COLLEGE OF PHARMACY 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 1
  • 2. CONTENT 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 2 INTRODUCTION ADVANTAGES DISADVANTAGES TYPES LIPOSOMES AND CANCER MARKETED FORMULATIONS
  • 3. TARGETING METHODS • Rational Research in drug delivery began in 1950s. • Need for Targeted/controlled Drug Delivery: Delivery of the drug at a rate and/or a location dictated by the needs of the body or disease state over a specified period of time. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 3
  • 4. LIPOSOMES • Liposomes is Greek words means ‘Lipo’ mean ‘Fat’ and ‘Somes’ mean ‘Body’. • 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 are extensively used as carriers for numerous molecules in cosmetic and pharmaceutical industries. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 4
  • 5. • Discovered in 1960‟s by Bangham and coworkers. • The size range of liposome: 20 nm up to several micrometers. • Due to their size and hydrophobic and hydrophilic character(besides biocompatibility), liposomes are promising systems for drug delivery. • The choice of bilayer components determines the ‘rigidity’ or ‘fluidity’ and the charge of the bilayer. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 5
  • 6. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 6
  • 7. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 7
  • 8. COMPOSITION OF LIPOSOMES There are number of components of liposomes however Lecithin (mixture of phospholipids) and cholesterol being main components. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 8
  • 9. PHOSPHOLIPIDS Phospholipids are fatty substances the major structural components of cell wall & biological membranes. Phospholipids are amphipathic moieties with a hydrophilic head group and two hydrophobic tails. Two types of phospholipids exist – PHOSPHODIGLYCERIDES AND SPHINGOLIPIDS, together with their corresponding hydrolysis products. • Phospholipids have phosphatidyl moiety (tail) with different head groups (choline, Ethanolamine, Serine) • The most common phospholipid is Phosphatidylcholine (PC) molecule. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 9
  • 10. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 10 Phosphatidylcholine has glycerol bridge links a pair of hydrophobic acyl hydrocarbon chains having 10-24 carbon atoms with a hydrophilic polar head group.
  • 11. ADVANTAGES • Provides selective passive targeting to tumor tissues (liposomal doxorubicin). • Increased efficacy and therapeutic index. • Increased stability via encapsulation. • Reduction in toxicity of the encapsulated agent. • Improved pharmacokinetic effects (reduced elimination, increased circulation life times). • Flexibility to couple with site-specific ligand to achieve active targeting. • Site avoidance effect (avoids non-target tissues). 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 11
  • 12. DISADVANTAGES • Very high production cost. • Drug leakage/ entrapment/ drug fusion. • Sterilization. • Short biological activity / t ½. • Oxidation of bilayer phospholipids. • Repeated iv administration problems. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 12
  • 13. STERILIZATION OF LIPOSOMES • Due to the particular sensitivity of liposomes and their tendency to physicochemical alterations, their sterilization remains a real challenge. Conventional sterilization methods such as heat, ethylene oxide, ultraviolet and gamma irradiations are considered as unsuitable for liposome sterilization. • The search for an alternative method being therefore necessary, the applicability of SUPERCRITICAL CARBON DIOXIDE (ScCO2) TECHNOLOGY, which is nowadays a promising strategy for the sterilization of sensitive products such as liposomes. ScCO2 could effectively be an interesting alternative to achieve sterility of liposomes. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 13
  • 14. TYPES 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 14 BASED ON METHOD OF PREPARATION BASED ON STRUCTURAL PARAMETERS BASED ON COMPOSITION AND APPLICATION CLASSIFICATION LIPOSOMES CAN BE CLASSIFIED BASED ON THREE DIFFERENT CRITERIA:
  • 15. CLASSIFICATION OF LIPOSOMES 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 15 BASED ON STRUCTURAL PARAMETERS MLV Multilamellar Vesicles (>0.5 μm) OLV Oligolamellar Vesicles (0.1 – 1 μm) UV Unilamellar Vesicles (Full size range) SUV Small Unilamellar Vesicles (20 – 100 nm) GUV Giant Unilamellar Vesicles ( >1 μm) MUV Medium Unilamellar Vesicles LUV Large Unilamellar Vesicles (>100 nm) MVV / MV Multivesicular Vesicles (>1 μm)
  • 16. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 16
  • 17. BASED ON COMPOSITION AND APPLICATION CL ( Conventional liposomes) Neutral/ Negatively charged phospholipids and cholesterol Fusogenic Liposomes RSVE – Reconstituted Sendai Virus Envelop pH sensitive Liposomes Using phospholipids such as PE or DOPE with OA Cationic Liposomes Cationic Lipids with DOPE Long Circulatory ( stealth) Liposomes ( LCL) High Tc made using cholesterol and 5 – 10% PEG – DSPE or GM1 Immuno – liposomes With attached monoclonal antibody 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 17
  • 18. BASED ON METHOD OF PREPARATION DRV dehydrated – Rehydration method VET Vesicle prepared by extrusion technology REV SUVs/ OLVs made by reverse – phase evaporation method FAT MLV Frozen and Thawed MLVs MLV- REV MLVs made by reverse phase evaporation method SPLV stable plurilamell ar Vesicles 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 18
  • 20. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 20 TRANSFEROSOMES ARCHEOSOMES VIROSOMES ETHOSOMES
  • 21. MARKETED FORMULATIONS CARRIER SYSTEM TARGETED SITE CARRIER FORMULATION MARKETED EXAMPLES IV TUMOR CELL LIPOSOMES POWDER , DISPERSION AND SOLVENT FOR CONCENTRATE FOR DISPERSION FOR INFUSION myocet IV FUNGAL CELL WALL LIPOSOMES POWDER FOR DISPERSION FOR INFUSION AmBisome® 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 21
  • 22. LIPOSOMES AND CANCER • Liposomes have revolutionized cancer therapy by their broad clinical applications. • Liposomes overcome the limitations of conventional chemotherapy by improving the bioavailability and stability of the drug molecules and minimizing side effects by site-specific targeted delivery of the drugs. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 22
  • 23. Biological Challenges Facing Liposomal Drug Delivery Systems As with any foreign particle that enters the body, liposomes encounter multiple defense systems aimed at recognition, neutralization, and elimination of invading substances. These defenses include the RES (Reticuloendothelial system), opsonization, and immunogenicity. While these obstacles must be circumvented for optimal liposome function, other factors such as the enhanced permeability and retention (EPR) effect can be exploited to enhance drug delivery. 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 23
  • 24. REFERENCES • Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S. et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett 8, 102 (2013). https://doi.org/10.1186/1556-276X-8-102 • Sriram Vemuri, C.T Rhodes, Preparation and characterization of liposomes as therapeutic delivery systems: a review, Pharmaceutica Acta Helvetiae, Volume 70, Issue 2, 1995, https://doi.org/10.1016/0031-6865(95)00010-7 • Nina Filipczak, Jiayi Pan, Satya Siva Kishan Yalamarty, Vladimir P. Torchilin, Recent advancements in liposome technology, Advanced Drug Delivery Reviews, Volume 156, 2020, 4-22, https://doi.org/10.1016/j.addr.2020.06.022 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 24
  • 25. THANK YOU! 12-07-2022 Department of Pharmaceutics, KMCH College OF Pharmacy 25