The name liposome is derived from two Greek words: Lipo meaning “fat” and Soma meaning “body”.
Liposome are also defined as artificial microscopic vesicles consisting of aqueous compartment and surrounded by one or more concentric layer of phospholipid.
The sphere like interior encapsulates a liquid and also contain more substance like peptides, protein, hormones, enzymes, antibiotic, antifungal and anticancer agents.
1. LIPOSOMES
Presented by
Punith M
M. Pharm, 2nd Semester
Molecular pharmaceutics(NTDS)
Department of Pharmaceutics
Acharya & BM Reddy College of Pharmacy, Bengaluru
1
2. INTRODUCTION
• The name liposome is derived from two Greek words: Lipo meaning
“fat” and Soma meaning “body”.
• Liposome are also defined as artificial microscopic vesicles consisting
of aqueous compartment and surrounded by one or more concentric
layer of phospholipid.
• The sphere like interior encapsulates a liquid and also contain more
substance like peptides, protein, hormones, enzymes, antibiotic,
antifungal and anticancer agents.
• The size of a liposomes ranges from some 20nm up to several
micrometers and the thickness of each phospholipid layer is about
4nm. 2
4. COMPOSITION OF LIPOSOMES
• Liposome are most often composed of - phospholipid and cholesterol.
Phospholipid- It is major structural component of liposome. It has the
characteristic of excellent biocompatibility and amphiphilic in nature.
There exists two sorts of phospholipid – Glycerophospholipids and
sphingolipids.
Examples of phospholipid:- Phosphatidyl choline (Lecithin) – PC,
Phosphatidyl ethanolamine (cephalin) – PE, Phosphatidyl serine (PS),
Phosphatidyl inositol (PI) and Phosphatidyl glycerol (PG).
4
5. Cholesterol - Cholesterol is one of the other components present in
liposome. Cholesterol does not itself form bilayer structure but can be
incorporated into phospholipid membranes in very high concentration.
It acts as fluidity buffer.
• The concentration of cholesterol is affecting the particle size of
liposome, improving the stability of the vesicle and preventing the
aggregation of molecules.
5
6. PROPERTIES OF LIPOSOMES
Some of the properties of liposomes imparted due to their structural
characterization and organization are:
• They are amphiphilic.
• They are permeable to water.
• Osmotically, they are sensitive.
• The liposomes with positively charged membranes are impermeable to
cations, and those containing negative charges are relatively permeable
to anions.
6
7. PHASE TRANSITION TEMPERATURE OF LIPOSOME
• Phase transition temperature (Tc) is temperature at which a membrane
changes between the fluid and gelled state. Phase transition of lipid
bilayer is a important property of liposome.
• Liposome with low Tc (less than 37°C) are fluid like and result
leakage of drug content at physiological temperature. But, the high Tc
(greater than 37°C) of liposomes is rigid and less leakage possibility at
physiological temperature.
• The transition from one phase to another can be detected by technique
like micro-calorimetry.
7
8. LIPOSOME CELL INTERACTION/MECHANISM
• The adsorption and endocytosis are the two main mechanisms for
liposomes cell interaction.
• Liposomes can be adsorbed to a cell surface directly (non-specifically)
or by specific interaction with a cell-surface receptor.
• To achieve specificity, liposomes can be derivatized with protein,
antibody, or carbohydrates moieties or with other polymers.
• In endocytosis, the target cell internalizes the liposomes actively.
• In addition to adsorption and endocytosis, there are two other
categories of liposome interaction with the cell surface; fusion of the
cell with the vesicle, and lipid exchange.
8
9. ADVANTAGES OF LIPOSOMES
1) Can carry both water and lipid soluble drugs.
2) Non-ionic in nature.
3) Liposome is biocompatible, completely biodegradable, non-toxic,
and non-immunogenic.
4) Suitable for delivery of hydrophobic, amphipathic and hydrophilic
drug.
5) Protect encapsulated drug from the external environment.
6) Liposome reduces toxicity and increase stability via encapsulation.
7) They are increase activity of chemotherapeutic drug.
9
10. 8) Biodegradable drug can be stabilized from oxidation.
9) Reduce exposure of sensitive tissues to toxic drugs.
10) Improve protein stabilization.
11) Control hydration.
12) Provide sustained release.
13) Targeted drug delivery or site specific drug delivery.
14) Can be administered through various routes.
10
11. DISADVANTAGES
1) Production cost is high.
2) Leakage and fusion of encapsulated.
3) Short half-life.
4) Stability problems.
5) Allergic reaction may occur to liposome constituents.
6) Problem to targeting to various tissues due to their large size.
7) Phospholipid undergoes oxidation, hydrolysis.
11
12. CLASSIFICATION OF LIPOSOMES
1) Classification of liposome depending upon size and shape
a) Multilamellar vesicles (MLV)
b) Large unilamellar vesicles (LUV)
c) Small unilamellar vesicles (SUV)
2) Classification of liposome according to composition
a) Conventional liposome
b) pH- sensitive liposome
c) Cationic liposome
d) Long circulating/Stealth liposomes
12
13. e) Immuno- liposome
f) Transferosomes
g) Ethosomes
h) Virosomes
i) Archaeosomes
j) Multivesicular Liposomes
3) Classification of liposome depending upon production method
A) Passive loading technique
B) Mechanical/Physical dispersion technique
a) Sonication
b) Lipid hydration by hand shaking or freeze drying 13
14. c) Micro emulsification
d) French pressure cell
e) Membrane extrusion
f) Dried reconstituted vesicles (DRVs)
g) Fusion method
h) Freeze and thaw extrusion method (FAT)
C) Solvent dispersion technique
a) Ether injection
b) Ethanol injection
c) De-emulsification method
d) Rapid solvent-exchange method
14
16. 1) DEPENDING UPON SIZE AND SHAPE
a) Multilamellar vesicle (MLV) - Multilamellar vesicle are generally
size between '100- 1000 nm' and it consist of two or more than two
bilayers.
• The method of preparation of multilamellar vesicle is very simple,
which include in thin- film hydration method/ hydration of lipids in
excess of organic solvent.
• They are very long storable because they are mechanically stable. It is
rapidly cleared by "Reticulo-Endothelium System" (RES) cell.
b) Large unilamellar vesicle (LUV) - The large unilamellar vesicles of
liposome consist of a single bilayer or single lamella. LUV size is > 100
nm and can reach size up to 1000 nm. 16
17. • They have mainly high efficiency of encapsulation, since ability to
hold large volume of solutions in their cavity.
• They are similar to multilamellar vesicle. Large unilamellar vesicles
are prepared from various methods like ether injection, reverse phase
evaporation technique and detergent dialysis.
c) Small unilamellar vesicle (SUV) - Small unilamellar vesicles are
generally smaller size (< 50 nm) as compared to multilamellar vesicle
and large unilamellar vesicle.
• Small unilamellar vesicles contain single bilayer. SUV are prepared
from solvent injection method (ethanol and ether injection).
17
18. 18
Fig 2 :- Liposomes classification based on size
and shape
19. 2) CLASSIFICATION OF LIPOSOME DEPENDING UPON
COMPOSITION/ LIPOSOME DERIVED VESICLES
a) Conventional liposome
• Conventional liposome is composed of natural phospholipid or lipid
such as sphingomyelin, egg phosphatidylcholine.
• Liposome containing positive and negative charge have been reported
to have shorter half- lives, toxic and rapidly remove from systemic
circulation.
• These liposomes are mainly use for targeting of the
'Reticuloendothelial system'(RES). Conventional liposome is used
mostly as compare to other types because it has shorter circulation
times.
• To increase circulation time, liposome surface can be coated with a
hydrophilic polymer.
19
20. b) pH- sensitive liposome
• pH- sensitive liposome is composed of oleic acid (OA), phosphatidyl
ethanolamine (PE), cholesterol hemisuccinate(CHEMS).
• pH- sensitive liposomes are stable at physiological pH (pH- 7.4)
• pH- sensitive liposomes are lipid composition that can be destabilized
when the external pH is changed from neutral or slight alkaline pH to
an acidic pH. In cell culture pH sensitive liposome can increase the
delivery of proteins, fluorescent markers, cytotoxic substance, RNA
and DNA into the cytoplasm.
20
21. c) Cationic liposome
• Cationic liposomes are composed of dimethyl-dioctaatidecyl ammonium
bromide (DDAB), 1,2-di mrystyloxypropyl-3-dimethyl-hydroxethyl
ammonium bromide (DORIE) combined with dioleoylphosphatidyl
ethanolamine (DOPE) etc.
• These liposomes are highly toxic and have short lifespan, thus limited to
local administration. They are mostly use for delivery of
macromolecules (negatively charge) and delivery of DNA and RNA.
21
22. d) Long circulating liposome (Stealth liposomes)
• These are the carrier systems that can avoid phagocytosis and, thus
circulate longer in the blood.
• Long circulating liposome are prepared by coating liposome surface
with a hydrophilic layer of oligosaccharides, glycoproteins, synthetic
polymers, which prevent opsonization.
• Long circulating liposome are widely use in biomedical in-vitro and
in-vivo studies and clinical practice. The liposome is very useful tools,
especially for tumor targeting therapy. Long circulating liposome
exhibit dose-independent, non-saturable, long-linear kinetics and
increased bioavailability.
22
23. e) Immuno-liposome (ILs)
• This is a class of lipid vesicles designed for active targeting of their
encapsulated/entrapped material inside the body.
• The ILs posses moieties such as antibodies, carbohydrates and
hormones on the outer surface of their membrane.
• Recently, ILs have been used for gene targeting to human brain cancer
cells, which has resulted in a 70-80% inhibition in cancer cell growth.
23
24. f) Transferosomes
• Deformable liposomes (Transferosomes®) are the first generation of
elastic vesicles.
• They generally consist of phospholipids, cholesterol and additional
surfactant molecules, such as sodium cholate. Transferosomes are
ultradeformable and squeeze through pores less than one-tenth of their
diameter.
g) Ethosomes
• These are high ethanol containing vesicles, most widely used in
transdermal or topical delivery due to its physicochemical
characteristics, more efficiently across the skin barrier and reach into the
systemic blood circulation.
24
25. h) Virosomes
• Virosomes or artificial viruses are one type of liposome that contain
reconstituted viral proteins in their structure. Unlike viruses,
virosomes are not able to replicate but are pure fusion-active vesicles.
• Due to the presence of the specialized viral proteins on the surface of
virosomes, they can be used in active targeting and
delivery/controlled release at the desired /specific/target site.
• Viruses have developed the ability to fuse with the cells during the
course of evolution, thus allowing for release of their contents directly
into the cells.
Ex: Epaxal is an aluminium-free vaccine based on formalin-inactivated
hepatitis A (strain RG-SB) antigen incorporated virosomes.
25
26. i) Archaeosomes
• They are defined as liposomes made from one or more of the polar
ether lipids extracted from the domain Archaea (Archaeobacteria).
• Many archaea live in environments including high salt concentration
or low pH values and high temperatures. Hence, their membrane lipids
are unique and enable them to survive in such hostile conditions.
j) Multivesicular Liposomes
• They are composed of several small vesicles entrapped by a single
lipid bilayer. MVLs prepared by a multiple emulsion method possess a
unique structure of multiple, non-concentric, aqueous chambers
surrounded by a network of lipid membrane.
26
27. 3) CLASSIFICATION OF LIPOSOMES DEPENDING UPON
PRODUCTION METHOD
A) Passive loading technique
• Passive loading is in which liposome are formed concurrently with
drug loading. In that hydrophilic compounds are distributed
homogeneously in the aqueous phase (both inside and outside the
liposomes) and hydrophobic drugs are retained inside the lipid bilayer
of liposome.
27
28. B) MECHANICAL/PHYSICAL DISPERSION TECHNIQUE
a) Sonication
• Sonication is a process in which sound waves are used to agitate
particle in solution. Such disruption can be used to mix solutions,
speed the dissolution of a solid into a liquid and remove dissolved gas
from liquid. Sonication is method in which MLVs are transformed to
small unit lamellar vesicles (SUVs). The ultrasonic irradiation is
provided to convert MLVs to SUVs. There are two method used,
28
29. 1) Bath sonication method
• The liposome dispersion in a cylinder is placed into a bath sonicator.
• Controlling the temperature of the lipid dispersion is usually easier.
2) Probe sonication method
• The tip of a sonicator is directly engrossed into the liposome
dispersion.
• The energy input into lipid dispersion is very high.
• The coupling of energy at the tip results in local hotness, the vessel
must be engrossed into a water/ice bath.
29
31. b) Lipid film hydration
• It is the most widely used method for the preparation of MLVs and can
be performed in two steps:-
Step (1) - Lipid hydration by hand shaking
• The lipids are dissolved in chloroform: methanol (2:1 v/v) solvent
mixture. Then introduce into a round bottom flask. This flask is
attached to rotary evaporator (rotated at 60 rpm).
• The organic solvent is evaporated at about 30° C or about transition
temperature of lipid. The evaporator is placed in vacuum source to
eliminate residual organic solvent. Remove the flask from the
evaporator and place on ice to obtain thin lipid film and lyophilize
until dry.
31
32. Step (2) - Hydration of lipid layer
• After removal from lyophilizer, 5ml saline phosphate buffer is added.
The flask is again attached to evaporator. The evaporator are rotated at
room temperature and pressure at same speed (for below 60 rpm).
• The flask is rotated for 30 minute or until all lipid has been removed
from the wall of the flask and has given homogeneous milky
suspension.
• The suspension is allowed to stand for 2 hours at room temperature or
at a temperature above transition temperature of the lipid in order to
complete the swelling process to give MLVs (Multilamellar vesicle).
32
34. c) Microemulsification
• SUVs can be prepared from concentrated lipid suspension by the use
of a microfluidizer. It yields liposomes with good aqueous phase
encapsulation.
• The vesicle dispersion is forced in microfluidizer pump through a 5µm
screen at very high pressure. Subsequently, vesicle dispersion is forced
through specific micro channels, which direct two streams of vesicle
dispersions to strike at right angles with very high velocity.
• The vesicle dispersion collected can be used again in the pump and
interaction chamber until spherical vesicles are achieved.
34
35. 35
Fig 6 : - Microemulsification using
microfluidizer
36. d) French pressure method
• This method is used to disrupt the plasma membrane of cells by
passing them through a narrow valve under high pressure (20,000 psi
at 40°c).
• This method used to preparation of 1-40 ml of homogeneous
unilamellar liposomes of intermediate size (30-80 nm). This liposome
is more stable compared to the sonicated liposomes.
• This method has some drawbacks which are, initial high cost for the
pressure cell. Liposome prepared by this method have less structural
defects compared to sonicated liposome.
36
38. e) Membrane extrusion
• Lipid suspension is forced through a polycarbonate filter of a defined
pore size to yield particles having a diameter near the pore size of the
filter used.
• Prior to extrusion through the final pore size, LMV are disrupted either
by several freeze-thaw cycles or by prefiltering the suspension through
a larger pore size. This method improves the homogeneity of the size
distribution of the final suspension.
• The extrusion should be done at a temperature above the Tc of the
lipid.
38
40. f) Dried reconstituted vesicles
• This method involves freeze drying the dispersion of empty SUVs,
followed by rehydration with the aqueous fluid, which have material to
be entrapped giving rise to dispersion of solid particles in finely
subdivided form.
• Advantages - High entrapment of water soluble component and use of
gentle situation for preparing liposomes.
• This method id appropriate only for SUVs, since there is low rate of
incorporation of MLVs.
g) Fusion method
• In this process, fusogenic agents are used for fusion of SUVs for
increasing the entrapment efficiency.
• This method allows the protection of lipid and entrapped material from
harmful physicochemical environment.
40
41. • Alteration in the pH increases the surface charge density of lipid bilayer
and brings on spontaneous vesiculation.
• Aggregation can also be induced by using calcium.
h) Freeze and thaw extrusion method (FAT)
• In this method, liposomes formed using the thin-film method are
vortexed with the material needed to be incorporated in the vesicles.
This is done until the whole lipid film is suspended. Then, the resulting
vesicles are frozen in warm water and vortexed again.
• This is the most preferable technique when it comes to the formation of
multilamellar vesicles or increasing the encapsulation efficiency of the
liposomes.
41
42. C) SOLVENT DISPERSION METHOD
• Firstly, dissolving the lipid and other constituents of the liposome
membrane in other solution(organic solvent). Then, the aqueous phase
is added to resulting solution. In this aqueous phase contain material
which is to be entrapped.
• Solvent dispersion method involving ether injection method, ethanol
injection method, and reverse phase evaporation method.
a) Ether injection method
• Solution of lipid is dissolved into ether or diethyl ether or methanol
mixture.
42
43. • These mixtures are slowly injected into aqueous solution of the
material to be encapsulation at 55-65°C or under reduce pressure.
Then ether is removed with the help of vacuum leads to formation of
liposome.
b) Ethanol injection method
• This is simple method. In this method an ethanol solution of the lipid
is directly injected rapidly to an excess of saline through a fine needle.
The rate of injection is kept enough to attain absolute and rapid
mixing; subsequently ethanol is diluted immediately with water.
• This leads to equal dispersion of phospholipids throughout the
medium. This procedure yields a high proportion of SUVs (about 25
nm diameter).
43
45. c) De-emulsification method
• Involves formation of first the inner leaflet of bilayer, followed by
outer half. Aqueous medium comprising material to be entrapped is
added into higher volume of immisicible organic solution of lipid.
• This leads to formation of w/o emulsion, which is subsequently
agitated mechanically to break aqueous medium into microscopic
water droplets ; the droplets are stabilized by means of phospholipid
monolayer on the interface.
45
46. d) Rapid solvent-exchange method
• This method involves the rapid transfer of lipid mixture between pure
solvent and pure aqueous environment. The lipid solution in organic
solvent is passed through an orifice of syringe by means of vacuum
into a tube containing aqueous buffer, which is placed on a vortexer.
• Before coming in contact with aqueous phase, the organic solvent gets
vaporized due to vacuum and eliminated very rapidly in few seconds.
Simultaneously, the lipid mixture also precipitates in aqueous buffer
very quickly.
46
47. e) Double emulsion method
• The organic solution containing water droplets (w/o) is brought in
contact with an excess of aqueous medium, followed by mechanical
dispersion, which results in phase inversion and formation of multi-
compartment vesicles takes place (w/o/w).
• These vesicles are suspended in aqueous medium, in which the two
aqueous compartments are separated from each other by means of two
phospholipid monolayers. The hydrophobic surfaces of monolayers
face each other transversely by a thin film of organic solvent.
• Elimination of the organic phase causes formation of intermediary
sized unilamellar vesicles.
47
48. f) Reverse phase evaporation method
• The mixture of two phases is subjected to bath sonication. It contains
phospholipid in organic solvent(diethyl ether) and aqueous buffer.
• The droplets, thus formed, are dried down to a semi-solid gel under
reduced pressure by a rotary evaporation.
• The monolayers of phospholipid at this stage surround each water
compartment, which is closely opposed to each other. This is followed
by mechanical shaking with the help of vortex shaker causing collapse
of certain water droplets. During this process, the lipid monolayer,
which enclosed the collapsed vesicle, becomes the part of adjacent
vesicle to form outer leaflet of bilayer of LUVs.
• Dispersion medium for this newly formed liposomes is provided by
the aqueous content of collapsed droplets.
48
50. D) DETERGENT SOLUBILIZATION/ REMOVAL METHOD
• In this, the phospholipids are bought in intimate contact with the aqueous
phase via detergents, which associate with phospholipids molecules. The
structures formed due this association are called as ‘micelles’. Upon
removal of detergent, LUVs may be formed (Homogenous size liposomes
are obtained).
• The shape and size of the micelles depends on the chemical nature of the
detergent, concentration and other lipids involved. Critical Micelle
Concentration (CMC) is the concentration of detergent in water at which
micelles begin to form. Below CMC detergent molecules remains in free
solution.
• Detergent removal is done by dialysis system, gel chromatography using
Sephadex G-25 column, adsorption/binding of triton x-100 and binding of
octyl glucoside. 50
51. E) ACTIVE LOADING TECHNIQUE
• In this method, internalization of preformed liposomes is typically
driven by a trans-membrane pH gradient. The pH surrounding the
liposome allows some of the drug to remain in unionized form, hence,
allowing it to migrate across the bilipid layer. Once, inside the
liposomes, the drug becomes ionized and gets entrapped here due to
the difference in pH.
51
52. Advantages of active loading method over passive encapsulation
techniques are-
• A high encapsulation efficiency and capacity.
• A reduced leakage of encapsulated compounds.
• Limited chemical degradation during storage.
• Avoidance of biological active compounds during preparation steps
in the dispersion thus reducing safety hazards.
52
53. EVALUATION OF LIPOSOME
1) Physical characterization: - Physical characterization evaluates
various parameters include size, shape, surface features, release
profile and phase behaviors.
2) Chemical characterization: - It includes study of purity and potency
of various lipophilic constituents.
3) Biological characterization: - They are useful in safety and
suitability of formulation for therapeutic application.
53
55. STABILITY OF LIPOSOMES
• The stability can be determined by storage under the following
conditions:-
1. Highest and lowest temperatures likely to be encountered, for one
month
2. Room temperature for 12-24 months
3. Two or three freeze-thaw cycles (20-25°C)
4. 60 cycles/min on a reciprocating shaker for 24-48 hrs
5. Six to eight heat-cool cycles (5-45°C, 48 hrs at each temperature)
6. Visual or microscopic examinations
After storage at these conditions, the liposomes are evaluated for the
residual drug content, vesicular size and shape and number of vesicles
per cubic mm. 55
56. APPLICATION
1) Site-specific drug delivery: Liposomes are suitable vehicles for drug
delivery at targeted locations. To form a site-specific drug delivery
system, they are combined with opsonins and ligands, such as
antibodies, sugar residues, apoproteins, or hormones, which are tagged
on the lipid vesicles. This also helps in reducing drug-related toxicity.
2) As artificial blood surrogates: Liposome encapsulated haemoglobin
products are being investigated as artificial RBCs (oxygen carrying
RBCs substitutes). Sterically stabilized liposomes bearing haemoglobin
are better than conventional liposomes encapsulating haemoglobin.
These systems have manifest toxicity, less platelet activation and
aggregation and less haemostatic generation.
56
57. 3) Treatment of parasitic diseases and infections: Liposomes serve as
an ideal carrier to deliver the drugs to treat parasitic diseases, especially
those that infect monocytes and macrophages cells, like leishmania.
4) Agriculture industry: Liposomes can entrap unstable compounds
such as antimicrobials, flavors, antioxidants, and bioactive elements and
protect them from a variety of environmental and chemical changes,
such as enzymatic chemical changes, ionic strength variations, and
temperature change. Thus, they are used to develop new flavors, control
flavor release, improve food color, and modify the texture of food
components. It also ensures the release of the ingredients at the desired
time.
57
58. 5) HIV (human immunodeficiency virus) infection
treatment: Liposomes can encapsulate anti-HIV nanocarriers, like
antiretroviral nucleotide and other antiviral drugs, and deliver them to
specific sites.
6) Transdermal drug delivery: The main challenge in transdermal drug
delivery is the penetration of macromolecules and hydrophilic drugs
through the stratum corneum (outer layer of the skin). Liposomes have a
similar molecular composition as lipid layers and have high permeability.
Thus, they are a suitable carrier for the delivery of drugs penetrating the
skin.
7) Enzyme immobilization: Liposomes can deliver the enzymes to the
lysosomal system or to the other sites. β-glucosidase and α-glucosidase
can be immobilized in liposomes, for the treatment of Gaucher's disease
(lysosomal storage disease) and Pompe or acid maltose disease (glycogen
storage disease type II), respectively.
58
59. 8) Liposomes in ocular delivery
• Liposomes are also used in ocular delivery because they are capable in
developing intimate contact with ocular tissues (cornea and
conjunctiva) and hence, provide higher drug absorption.
• Liposomes also provide protection to the drug from metabolic
enzymes present in tear and/or at corneal epithelium and also
improved ocular bioavailability and patient compliance by reducing
dosing frequency.
• Liposomes can deliver both hydrophilic and lipophilic drugs, such as
Pilocarpine, Ofloxacin, Diclofenac sodium, Ganciclovir and
Chloramphenicol. The cationic surface charge liposomes exhibit
excellent corneal uptake in comparison to anionic and neutral
liposomes.
59
60. 9) Tumour therapy
• Liposome delivery systems offer the promising potential to enhance
the therapeutic index of anticancer drugs, either by increasing the drug
concentration in tumour cells or by decreasing the exposure in normal
host tissues.
• Liposomes can be injected intravenously. When they are modified
with lipids, which render their surface more hydrophilic, their
circulation time in the bloodstream can be increased significantly. In
this form they can extravasate to the tumour vascular endothelium.
These so-called “stealth liposomes” are especially being used as
carriers for hydrophilic (water soluble) anticancer drugs like
Doxorubicin, Mitoxantrone and others.
• The Myocet(Metastatic breast cancer) and Doxil® are the two first
approved liposomal formulations and both contain doxorubicin but
differ particularly the presence of Polyethylene glycol (PEG) coating.
60
61. 61
Compound Target Company
TLC ELL-12 Various solid tumours Liposome Company Inc.,
Princeton, New Jersey
Ambisome Fungal infection Gilead Sciences, Foster City,
California (CA)
Caelyx Metastatic breast and ovarian
cancer
North Ryde, New South Wales
LipoTaxen Lung, breast and ovarian cancer Lipoxen, London, UK
Lipo-DOX® Kaposi’s sarcoma Sun Pharma Advanced
Research Centre, Vadodra,
India
VincaXome Solid tumours NeXstar, California, USA
Depocyt Cancer therapy Skye Pharm, London, UK
Table 2 : - Liposome formulations for
tumour therapy
62. 10) Liposomes as vaccine carriers: Liposomes potentiate both cell-
mediated and humoral immunity. Their advantages against other
adjuvants (detoxified cholera toxins, alum) can be summarized as:
(1) non-toxic, biocompatible and biodegradable;
(2) incorporate other adjuvants to provide strong immune response;
(3) convert loaded non-immunogenic substances into immunogenic
ones; and
(4) minimize or eliminate toxicity of toxic antigens and allergic
reactions to allergic patients.
• Liposomal vaccines investigated to date are based on
immunopotentiating reconstituted influenza virosome (IRIV). For
immunopotentiation, immunomodulating agents such as muramyl
dipeptide, lipopolysaccharide and lipid can be incorporated into
liposomes. 62
63. 63
Product Target Company
HepaXen Hepatitis B Lipoxen, London, UK
LipoNeu Streptococcus pneumoniac
causing meningitis
Lipoxen, London, UK
LipoRab Rabies Lipoxen, London, UK
Stimuvax Cancer cells Biomira Inc., Edmonton,
Canada
Influenza vaccine Influenza virus Crucell, Leiden, Netherlands
Avian retrovirus Chicken pox Vineland lab, Vineland, New
Jersey, USA
E. coli vaccine Escherichia coli Novavax, Rockville, USA
New castle disease vaccine New castle disease IGI, Vineland Lab, New Jersey,
USA
Shigella flexneri 2A vaccine Shigella flexneri 2A infections Novavax, Rockville, USA
Table 3 : - Liposome formulations as
vaccine carriers
64. 11) In gene delivery
• Lipid based systems, polymers, peptides and liposomes are non-viral
gene delivery vehicles. Among liposomes pH sensitive liposomes,
cationic liposomes, fusogenic liposomes, genosomes, lipoplex and
lipopolyplex seem to have gene delivery potential.
• The cationic liposomes deliver the content through membrane fusion
thereby avoiding lysosomal and nucleolus degradation of DNA. Some
of the widely used cationic liposomal formulations are Lipofectin,
Lipofectamine, Transfectase, Cytofectin and Transfectam.
• The pH-sensitive liposomes exploit the endosomal acidification to
promote fusion with endosomal memebranes.
64
65. • Genosomes are the complex formulations of DNA with various
cationic liposomes (lipoplex). Lipoplex has the tendency, to form
aggregate with DNA to form large and heterogeneous particles at high
concentration. To overcome this limitation, lipopolyplex formulations
composed of liposomes poly-cation/DNA are devised. Liposomal
DNA vaccination is one of the fast emerging as well as rewarding
areas.
12) As radiopharmaceutical and radio diagnostic carriers
• Liposomal radio-diagnostic applications include liver and spleen
imaging, lymphatic imaging, tumour imaging, blood pool imaging,
imaging cardiovascular pathologies, visualization of inflammation and
infection sites, brain visualization of bone marrow and eye
vasculature. Liposome based imaging agents have already been
successfully used for magnetic resonance, computed tomography and
ultrasound imaging of tumours.
65
66. 13) Cosmetics and dermatology
• Liposomes carrying skin-care material is an excellent addition to the
daily skin-care programs. Liposomes, when combined with essential
oil, provide an effective nourishing treatment that penetrates deeply
into the skin.
• Liposomes based anti-ageing topical formulations (creams, lotions,
gels and hydrogels) have been formulated and launched in the
cosmetic market in 1986 by L'Oreal in the form of niosomes and then
by Christian Dior in the form of liposomes.
• Liposomal preparations reduce the skin roughness because of its
interaction with corneocytes and of the intercellular lipids resulting in
skin softening and smoothening.
66
67. • Success rates of these products range between 83-98%, when
parameters, such as tightening and firming effects, texture,
smoothness, vitality, complexion, luminosity and clarity are
concerned. Various liposome based formulations for facial and body
care, make-up, mascara and foundations, hair care, self-tanning and
sunscreen products and perfumes are likely to be launched soon in the
market.
67
68. 68
Product/system Company Use
CaptureTM R60/80 Christian Dior, Paris, France Skin care and rejuvenation
PlenitudeTM L’Oreal, Paris, France Skin care and rejuvenation
Inovi Pharm/Apotheke, Gandijeva,
Beograd
Skin care and nourishment
Coatsome NCTM NOF America Corp. America Humectant
NactosomesTM Lancome(L’Oreal), Paris, France Rejuvenation and nourishment
NyotranTM Aronex Pharm, Texas, USA Systemic fungal infection
Mikasome® NeXstar, California, USA Bacterial infection
Table 4 : - Liposome formulations in cosmetics
69. REFERENCES
• Admin. A CONCISE REVIEW ON LIPOSOMES DRUG DELIVERY
SYSTEM [Homepage on the Internet]. PharmaTutor. Available from:
https://www.pharmatutor.org/articles/a-concise-review-on-liposomes-
drug-delivery-system
• Singh A. Liposomes: Structure, Classification, and Applications
[Homepage on the Internet]. Conduct Science. 2022;Available from:
https://conductscience.com/liposomes-structure-classification-and-
applications/
• N. K. Jain, Introduction to NOVEL DRUG DELIVERY SYSTEMS.
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