2. Contents
Introduction
Structure of phospholipid and liposomes
Advantages
Disadvantages
Classification
Method of preparation
Mechanism of preparation
Applications of liposomes
Evaluation of liposomes
Therapeutic application of liposomes
List of marketed product
Conclusion
Reference
3. Introduction
A spherical sac of phospholipid molecules.
Enclosing a water droplet (hydrophilic drug) and
Also have lipophilic drug in lipophilic portion.
Discovered in 1961 by Bangham and coworkers.
The structural main components are
phospholipids and cholesterol.
4. Structure of phospholipid
Phospholipids are amphipathic molecule.
They have a hydrophobic tail &
hydrophilic head.
The tail portion consist of 2 fatty acid
chains.
The head portion consist of phosphoric
acid.
5. Structure of liposomes
Formation of various types of vesicles depends on CPP.
CPP ( Critical packing parameter).
If CPP < 0.5 than liposomes are formed by hydrophobic
effect.
If CPP > 0.5 than liposomes are formed by hydrophilic
effect.
If CPP value is between 0.5-1.0 than the liposomes are
formed by surfactant effect.
6. How to calculate CPP
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 group.
7.
8. Advantages
Liposomes increased efficacy and therapeutic index of drug (actinomycin-D).
Liposome increased stability via encapsulation.
Liposomes are non-toxic, flexible, biocompatible, completely biodegradable,
and non-immunogenic for systemic and non-systemic administrations.
Liposomes reduce the toxicity of the encapsulated agent (amphotericin B,
Taxol).
Liposomes help reduce the exposure of sensitive tissues to toxic drugs.
Flexibility to couple with site-specific ligands to achieve active targeting.
9. Disadvantages
Sometimes phospholipid undergoes oxidation and hydrolysis-like reaction.
Leakage and fusion of encapsulated drug/molecules.
Production cost is high.
Fewer stables.
Short half-life.
10. Classification of liposome
Liposomes are classified on the bases of-
Structural parameter
Method of preparation
Composition and application
Conventional liposome
Specialty liposome
11. On the bases of structural parameter
Types of liposomes Structure
MLV (Multilamellar vesciles)
(300-5000nm)
OLV (Oligovascular vesciles)
(0.1-1.0µm)
12. ULV (Unilamellar vesciles)
(all size range)
a. MUV (Medium unilamellar vesciles)
b. SUV (Small unilamellar vesciles)
(20-100nm)
c. GUV (Giant unilamellar vesciles)
(>1.0µm)
Conti…
14. Based on the method of preparation
Method of preparation Types of preparation
Single or oligo lamellar vesicle made
by reverse phase evaporation method
REV
Multi lamellar vesicle made by reverse
phase evaporation method
MLV-REV
Stable pluri lamellar vesicle SPLV
Frozen and thawed multi lamellar
vesicle
FATMLV
Vesicle prepared by extrusion
technique
VET
Dehydration- Rehydration method DRV
15. Based on composition and application
Type of Liposome Abbreviation Composition
Conventional liposome CL Neutral or negatively
charge phospholipids and
cholesterol
Fusogenic liposome RSVE Reconstituted sendai virus
envelops
pH sensitive liposomes _ Phospholipids such as PER
or DOPE with either
CHEMS or OA
Cationic liposome _ Cationic lipid with DOPE
Long circulatory liposome LCL Neutral high temp,
cholesterol, and 5- 10%
PEG, DSP
Immuno liposome IL CL or LCL with attached
monoclonal antibody or
recognition sequences
17. Preparation of liposome
Rigidity of bi-layers is important parameter during preparation.
Various group of phospholipid use in preparation
Which are as follows-
1. Phospholipids from natural source
2. Phospholipids modified from natural source
3. Semi synthetic phospholipids
4. Fully synthetic phospholipids and
5. Phospholipids with natural head groups
23. Sonication
Bath sonication
A cylinder with liposome dispersion
placed into the bath sonicator.
Easy to control the temperature as
compare to the using probe
Probe sonication
The tip is directly engrossed into the
liposome dispersion.
Energy input in this method is very
high.
The coupling of energy at the tip result
in local hotness therefore the vessel
must be engrossed into the cold water
or N2.
33. Introduction
Hydrophilic, hydrophobic interaction between lipid-lipid, lipid-water molecules.
By input of energy ( sonication, homogenization, heating etc.)
Result- rearrangement into the form of bilayer vesicle.
Lasic et.al(2001) proposed that symmetric membrane prefer to be flat.
And energy required to curve them.
Sterols are determines the membrane curvature.
34.
35.
36.
37. Phospholipids ratio to be use in liposome
Phospholipid Ratio
DPPC:DOPC:Cholesterol 6:3:1
DPPC:DCP:Cholestrol 7:2:1
DOPC:Cholestrol 7:3
DOPE:CHEMS 7:3
mPEG2000:DSPE:DOPE:Cholestrol 6.5:0.5:3
mPEG2000:DSPE:HSPC:Cholestrol 0.5:5.5:4
aPEG2000DSPE:DOPE:CHEMS 6.5:0.5:3
39. 1. Liposome for Respiratory Drug Delivery
System
Liposomal aerosol has several advantages over ordinary aerosol.
1. Sustained release
2. Prevention of local irritation
3. Reduced toxicity and
4. Improved stability in the large aqueous core.
Several injectable liposomes are available in the market for lung targeting.
1. Ambisomes
2. Fungisomes and
3. Myocet.
Delivery of DNA can also be done through liposomes into the lungs.
41. Liposome in Eye Disorders
Liposomes can be use to treat disorder of both anterior and posterior segment.
includes dry eyes, keratitis, corneal transplant rejection, uveitis, endopthelmitis and
proliferative vitro retinopathy.
Liposome is used as vector for genetic transfection and monoclonal antibody directed
vehicle.
“Verteporfin” is approved drug for the ocular delivery of liposomes.
42. Liposome as Vaccine Adjuvant
firmly established as immuno-adjuvant.
Liposome acts as immuno-adjuvant by the following therapeutic points of view:
1. Liposomes as an immunological (vaccine) adjuvant
2. Liposomal vaccines
3. Liposomes as carrier of immuno modulation
4. Liposomes as a tool in immuno diagnostics.
It act by slowly releasing antigen or by passively accumulating into the lymph node.
It can be targeted into the lymphoid with the help of phosphotidyl serine.
43.
44. Liposomes for Brain Targeting
Liposomes with a small diameter (100 nm) as well as large diameter undergo free
diffusion through the Blood Brain Barrier (BBB).
SUVs couples with the brain drug transport vector to cross the BBB by the absorptive
mediated transcytosis.
cationic liposomes successfully undergo absorptive mediated endocytosis into cells.
addition of the sulphatide (a sulphur ester of galactocerebroside) to liposome
composition increases ability to cross BBB.
Wang et al. reported that mannose coated liposomes reach brain tissue and the mannose
coat assist transport of loaded drug through BBB.
polysorbate 85 recognize that it enhance the significance into the brain.
eg. Amitriptylline
45. Liposome as Anti-Infective Agents
Intracellular pathogen like protozoal, bacterial, and fungal remove by targeting the
liposome to their residence inside the body.
(ambisomes)
46. LIPOSOME IN TUMOUR THERAPY
The long term therapy leads to several toxic side effect.
The liposomal therapy for tumor targeting shows least side effect.
Small and stable liposome passively target the tissue and extra vasate in tissue with
long circulation.
Doxil is the liposomal formulation of doxorubicin (stealth liposome).
liposome which is prepared by several means. Caelyx and myocet are the liposomal
formulations of doxorubicin.
Caelyx is used for treatment of metastatic ovarian cancer but now in advanced breast
cancer.
Myocet s approved for metastatic breast cancer.
47.
48. Lymphatic targeting with liposomes
Because subcutaneous administration of liposomes results in their uptake by
draining lymphatic capillaries at the injection site.
Active capture of liposomes by macrophages in regional lymph nodes.
Liposome uptake by lymph nodes might be increased by using biotin-
bearing liposomes for preliminary injection.
Liposomes have been use for lymphatic delivery of methotrexate and
magnetic resonance imaging (MRI) with gadolinium (Gd)- loaded
liposomes.
56. 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.
