Presentation on liposome

1. LIPOSOMES
PRESENTED BY UNDER THE GUIDANCE OF
KASHMIRI SONOWAL ANANTA CHOUDHURY
M.PHARM ASSOCIATE PROFESSOR
FACULTY OF PHARMACEUTICAL SCIENCES FACULTY OF PHARMACEUTICAL SCIENCES
ASSAM DOWN TOWN UNIVERSITY ASSAM DOWN TOWN UNIVERSITY

2. CONTENT
 INTRODUCTION
 STRUCTURE OF LIPOSOME
 MECHANISM
 ADVANTAGES AND DISADVANTAGES
 CLASSIFICATION
 METHOD OF PREPARATION
 EVALUATION
 APPLICATION

3. INTRODUCTION
 Liposome are the small artificial vesicles of spherical shape that can be created
from cholesterol and natural non-toxic phospholipids. Due to their size and
hydrophobic and hydrophilic character, liposomes are promising systems for
drug delivery
 Liposome some properties differ considerably with lipid composition, surface
charge, size and the method of preparation.
 The choice of bilayer components determines the ‘rigidity’ or ‘fluidity’ and the
charge of the bilayer. For instance, unsaturated phosphatidylcholine species
from natural sources (egg or soybean phosphatidylcholine) give much more
permeable and less stable bilayers. whereas the saturated phospholipids with
long acyl chains (for example, dipalmitoylphos phatidylcholine)

4.  For instance, unsaturated phosphatidylcholine species from natural sources (egg or
soybean phosphatidylcholine) give much more permeable and less stable bilayers,
whereas the saturated phospholipids with long acyl chains (for example,
dipalmitoylphos phatidylcholine) form a rigid, rather impermeable bilayer structure.
STRUCTURE OF LIPOSOME:

5. MECHANISM
• In an aqueous environment the phospholipid orient themselves to form
bilayer where one layer of the phospholipid faces outside of the cells.
Whereas another layer of the phospholipid faces inside the cell to avoid
the water phase. The hydrocarbon tail of one layers faces the
hydrocarbon tail of another layer and combines to form bilayer this
structure is also called as lamella. Upon further hydration the lipid cake
(lamella) swells eventually that curves to form a closed vesicles in the form
of spheres known as liposome.

6. STRUCTURE OF PHOSPHOLIPID BILAYER

7. 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

8. DISADVANTAGES
• Low solubility
• Short half-life
• Sometimes phospholipid undergoes oxidation and hydrolysis-like
reaction
• Leakage and fusion of encapsulated drug/molecules
• Production cost is high
• Fewer stables

9. CLASSIFICATION
Based on
structural
paramet
ers
MLV
0.5
µ𝒎 OLV
0.1-1
µ𝒎
UV
(All size
range)SUV
30-70
nm
MUV
LUV
> 𝟏𝟎𝟎 µ𝒎
GUV
> 𝟏 µ𝒎

10. BASED ON
METHOD OF
PREPARATIO
NS
REV: reverse
phase
evaporation
vesicles MLV-REV:
Multi
lamellar
vesicle
DRV:
Dehydration-
rehydration
method
VET : vesicle
prepared by
extraction
method
SPLV: stable
plurilamellar
vesicles
FATMLV:
frozen and
thawed MLV
CLASSIFICATION

11. BASED ON
COMPOSITION
OF
APPLICATION
CL:
Conventi
onal
Liposom
e
Fusogeni
c
Liposom
es
PH
sensitive
Liposom
es
Cationic
Liposom
es
Long
circulato
ry
Liposom
e
Immuno
Liposome
s
CLASSIFICATION

12. METHOD OF PREPARATIONS
 PHYSICAL DISPERSION METHOD
1. HAND SHAKING MLVs
2. NON SHAKING LUVs
3. FREEZE DRYING
 TO REDUCE LIPOSOME SIZE
1. MEMBRANE EXCRUTION
2. ULTRA SONICATION
3. FRENCH PRESSURE CELL
4. MICRO-EMULSION

13.  TO INCREASE LIPOSOME SIZE
1. DRIED RECONSTITUTED VESICLES
2. FREEZE THAWING SONICATION
 SOLVENT DISPERSION METHOD
1. ETHANOL INJECTION
2. ETHER INJECTION
3. WATER ORGANIC PHASE
 DOUBLE EMULSION METHOD
 REVERSE PHASE EVAPORATION

14. HAND SHAKING MLVs:

15. NON-HAND SHAKING LUVs:

16. FREEZE DRYING METHOD:
• Multi lamellar vesicles can be prepared by freeze drying the most commonly
employed organic solvent.
• Freeze drying involves the removal of water from the product in the frozen state at
tremendously low pressure
• This method is mainly used to dry products that are thermoliable and would be
demolished by heat drying.
• For this technique generally t-butanol is used as its frezzing point exceeds the
operating temperature of the freeze dryer.
• Phospholipid are dissolved in t-butanol and the solution is freeze dried to obtain the
dried lipoid in foam like structure.
• Water or saline is added to dry lipid with through mixing to obtain MLVs.

17. MEMBRANE EXTRUSION:
• In this technique vesicles contents
are exchanged with dispersion
medium during breaking and
resealing of phosphate lipid
bilayar as they pass through
polycarbonate membrane.
• Less pressure is required here as
compare to French pressure cell.
• Use to process MLVs and LUVs.
• Two types of membrane one is
Tortuous and another is Nucleation
trach.

18. ULTRA SONICATION:
Sonication is the mostly used method
for the preparation of SUV. Here MLVs
are sonicated either with a bath type
sonicator and probe sonicator.
Disadvantages: this method is
contaminating the preparation with
metal which may lead to
degradation of the lipiid.(probe
sonicator)

19. FRENCH PRESSURE CELL:
• The method involves the extrusion of MLVs at 20,000 psi at 4 degree c
through a small orifice.
• In this technique the large vesicles rate converted to small vesicles under
high pressure.
• The technique yields uni or oligo lamellar liposome of intermediate size.
• The method has several advantages over sonication method. The
method is simple rapid, reproducible and involving gentle handling of
unstable materials. The resulting liposome are somewhat larger than
sonicated SUVs.
• The main drawback of the method are that the temperature is difficult to
achieve and the working volume are relatively small.

20. DRIED RECONSTITUTE VESICLE:
• In these process the dispersion of empty SUVs are freeze dried and
then these freeze dried SUVs is rehydrated with the aqueous fluid
containing the material to be entrapped.
• Which leads to the formation of solutes in uni or oligo lamellar
vesicles.

21. ETHANOL INJECTION:
• A lipid solution of ethanol is rapidly injected to a vast excess of buffer.
The MLVs are immediately formed. The drawbacks of the method are
that the population is heterogeneous (30-110 nm), liposomes are very
dilute, it is difficult to remove all ethanol because it forms azeo trope
with water and the possibility of various biologically active stability,
pyrogen control, sterility, size and size distribution and batch to batch
reproducibility

22. ETHER INJECTION:
• A solution of lipids dissolved in diethyl ether or ether/methanol
mixture is slowly injected to an aqueous solution of the material to
be encapsulated at 55-65°C or under reduced pressure. The
subsequent removal of ether under vacuum leads to the formation
of liposomes. The main drawbacks of the method are population is
heterogeneous (70-190 nm) and the exposure of compounds to be
encapsulated to organic solvents or high temperature.

23. REVERSE PHASE EVAPORATION VESICLE:
• First water in oil emulsion is formed by brief sonication of a two phase system
containing phospholipids in organic solvent (diethylether or isopropylether or
mixture of isopropyl ether and chloroform) and aqueous buffer. The organic
solvents are removed under reduced pressure, resulting in the formation of a
viscous gel. The liposomes are formed when residual solvent is removed by
continued rotary evaporation under reduced pressure. With this method high
encapsulation efficiency up to 65% can be obtained in a medium of low ionic
strength for example 0.01M NaCl. The method has been used to encapsulate small
and large macromolecules. The main disadvantage of the method is the exposure
of the materials to be encapsulated to organic solvents and to brief periods of
sonication.

24. EVALUATION
PHYSICAL
PROPERTIESS
Size and its
distribution
Surface charge
Percent capture
lamellarity
Drug release
Stability analysis

25. CHEMICAL
PROPERTIES
Phospholipid
concentration
Cholesterol
analysis
EVALUATION

26. APPLICATION
 CANCER THERAPY
 Liposome are successfully used to entrap anticancer drugs. This increases
circulation life time, protect from metabolic degradation
 LIPOSOME AS CARRIER OF DRUG IN ORAL TREATMENT
 Steroids used for arthritis can be incorporated into large MLVs.
 Alteration in blood glucose levels in diabetic animals was obtained by oral
administration of liposome encapsulated insulin.

27.  LIPOSOME FOR TOPICAL APPLICATION
 Drug like triamcinolone, benzocaine, corticosteroids etc can be
successfully incorporated as topical liposome.
 LIPOSOME FOR PULMONARY DELIVERY
 Inhalation devises like nebulizer are use to produce an aerosol of
droplets conataining liposome.
APPLICATION

28.  ENHANCED ANTIMICROBIAL EFFICASY OR SAFETY
Antimicrobial agents have been encapsulated in liposomes for two reasons.
 First, they protect the entrapped drug against enzymatic degradation. For
instance, the penicillins and cephalosporin are sensitive to the degradative
action of J-lactamase, which is produced by certain microorganisms.
 Secondly, the lipid nature of the vesicles promotes enhanced cellular
uptake of the antibiotics into the microorganisms, thus reducing the
effective dose and the incidence of toxicity as exemplified by the liposomal
formulation of amphotericin B.
APPLICATION

29. 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 drug delivery
system.

30. THANK YOU