This document provides an overview of liposomes, including their composition, mechanisms of formation, advantages, classifications, preparation methods, applications, and examples of marketed products. Liposomes are spherical vesicles composed of phospholipid bilayers that can encapsulate both hydrophilic and hydrophobic drugs. They are classified based on structural parameters like lamellarity and size, as well as composition. Common preparation techniques include thin film hydration, ethanol injection, sonication, and microfluidization. Liposomes are useful for targeted drug delivery to treat conditions like cancer and fungal infections, and some commercial liposome products are used to deliver drugs like amphotericin B and daunorubicin.
Liposomes, Structure of liposome, phospholipids, classification of liposomes, method of preparation of liposomes, mechanism of liposome formation, application of liposomes.
Liposomes, Structure of liposome, phospholipids, classification of liposomes, method of preparation of liposomes, mechanism of liposome formation, application of liposomes.
liposomes are novel drug delivery dosage systems, where the drug is entrapped in phospholipid bilayered vesicles. the release of drug from the vesicles can be controlled or sustained.
the follwing presentation contain structure, classification and preparation methods, characterization and applications of liposomes.
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Introduction
Structure
Niosomes Vs. Liposome
Advantages & Disadvantages
Properties of Niosomes
Method of Manufacturing
Evaluation of Niosomes
Applications
Marketed products
NIOSOMES , GENERAL CHARACTERISTICS OF NIOSOME , TYPES OF NIOSOMES , OTHERS TYPES OF NIOSOMES , NIOSOMES VS LIPOSOMES , COMPONENTS OF NIOSOMES , Non-ionic surfactant , Cholesterol , Charge inducing molecule , METHOD OF PREPARATION , preparation of small unilamellar vesicles , Sonication , Micro fluidization , preparation of large unilamellar vesicles , Reverse Phase Evaporation , Ether Injection , preparation of Multilamellar vesicles , Hand shaking method , Trans membrane pH gradient drug uptake process (remote loading) , Miscellaneous method :Multiple membrane extrusion method , The “Bubble” Method , Formation of Niosomes From Proniosomes , SEPARATION OF UNENTRAPPED DRUGS , Gel Filtration , Dialysis , Centrifugation , FACTORS AFFECTING THE PHYSICOCHEMICAL PROPERTIES OF NIOSOMES , Membrane Additives , Temperature of Hydration , PROPERTIES OF DRUGS , AMOUNT AND TYPE OF SURFACTANT
Structure of Surfactants , Resistance to Osmotic Stress , Characterization of niosomes ,Therapeutic applications of Niosomes , For Controlled Release of Drugs , To Improve the Stability and Physical Properties of the Drugs , For Targeting and Retention of Drug in Blood Circulation , Proniosomes , Aspasomes , Vesicles in Water and Oil System (v/w/o) ,Bola - niosomes , Discomes , Deformable niosomes or elastic niosomes , According to the nature of lamellarity ,Small Unilamellar vesicles (SUV) 25 – 500 nm in size.,Large Unilamellar vesicles (LUV) 0.1 – 1μm in size , Multilamellar vesicles (MLV) 1-5 μm in size , According to the size:Small Niosomes (100 nm – 200 nm) , Large Niosomes (800 nm – 900 nm),Big Niosomes (2 μm – 4 μm)
liposomes are novel drug delivery dosage systems, where the drug is entrapped in phospholipid bilayered vesicles. the release of drug from the vesicles can be controlled or sustained.
the follwing presentation contain structure, classification and preparation methods, characterization and applications of liposomes.
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Introduction
Structure
Niosomes Vs. Liposome
Advantages & Disadvantages
Properties of Niosomes
Method of Manufacturing
Evaluation of Niosomes
Applications
Marketed products
NIOSOMES , GENERAL CHARACTERISTICS OF NIOSOME , TYPES OF NIOSOMES , OTHERS TYPES OF NIOSOMES , NIOSOMES VS LIPOSOMES , COMPONENTS OF NIOSOMES , Non-ionic surfactant , Cholesterol , Charge inducing molecule , METHOD OF PREPARATION , preparation of small unilamellar vesicles , Sonication , Micro fluidization , preparation of large unilamellar vesicles , Reverse Phase Evaporation , Ether Injection , preparation of Multilamellar vesicles , Hand shaking method , Trans membrane pH gradient drug uptake process (remote loading) , Miscellaneous method :Multiple membrane extrusion method , The “Bubble” Method , Formation of Niosomes From Proniosomes , SEPARATION OF UNENTRAPPED DRUGS , Gel Filtration , Dialysis , Centrifugation , FACTORS AFFECTING THE PHYSICOCHEMICAL PROPERTIES OF NIOSOMES , Membrane Additives , Temperature of Hydration , PROPERTIES OF DRUGS , AMOUNT AND TYPE OF SURFACTANT
Structure of Surfactants , Resistance to Osmotic Stress , Characterization of niosomes ,Therapeutic applications of Niosomes , For Controlled Release of Drugs , To Improve the Stability and Physical Properties of the Drugs , For Targeting and Retention of Drug in Blood Circulation , Proniosomes , Aspasomes , Vesicles in Water and Oil System (v/w/o) ,Bola - niosomes , Discomes , Deformable niosomes or elastic niosomes , According to the nature of lamellarity ,Small Unilamellar vesicles (SUV) 25 – 500 nm in size.,Large Unilamellar vesicles (LUV) 0.1 – 1μm in size , Multilamellar vesicles (MLV) 1-5 μm in size , According to the size:Small Niosomes (100 nm – 200 nm) , Large Niosomes (800 nm – 900 nm),Big Niosomes (2 μm – 4 μm)
Liposomes by Mr. Vishal Shelke
https://youtube.com/vishalshelke99
https://instagram.com/vishal_stagram
Liposomes
Sub :- Novel Drug Delievery Systems, Sterile Products Formulation & Technology
M.Pharm Sem II
Savitribai Phule Pune University
Introduction :-
Liposomes are vesicular structures composed of a lipid bilayer. These vesicular structures can be used as a vehicle for administration of nutrients and drugs.
Liposomes are concentric bilayered vesicles in which an aqueous volume is entirely enclosed by a membranous lipid bilayer.
Liposomes consist of Cholesterol, Phospholipid and drug molecule
Classification of Liposomes :-
Small Unilamellar (SUV) [20-100nm]
Medium Unilamellar (MUV)
Large Unilamellar (LUV) [>100nm]
Giant Unilamellar (GUV) [>1μm]
Multi Lamellar Vesicles (MLV) [0.5nm]
Oligolamellar Vesicles (OLV)
Multi Vesicular (MV) [>1μm]
ADVANTAGES
Provides selective passive targeting to tumor tissues.
Increased efficacy and therapeutic index.
Increased stability via encapsulation.
Reduction in toxicity of the encapsulated agents.
Improved pharmacokinetic effects (reduced elimination, increased circulation life times).
DISADVANTAGES
low solubility
short half life
high production cost
less stability
leakage and fusion of encapsulated drug
sometimes the phospholipid layer undergoes oxidation and hydrolysis reaction
Methods of Preparation of Liposomes
1 Mechanical Dispersion Method
Lipid film hydration by
hand shaken MLVs
Micro emulsification
Sonication
French pressure cell
Dried reconstituted vesicles
Membrane Extrusion Method
2 Solvent Dispersion Method
Ethanol injection
Ether injection
Double emulsion vesicles
Reverse phase
evaporation vesicles
3 Detergent Removal Method
Vesicles are colloidal particles in which a concentric bilayer made-up of amphiphilic molecules surrounds an aqueous compartment Useful vehicle for drug delivery of both hydrophobic drugs and hydrophilic drugs, which are encapsulated in the interior aqueous compartment.
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Liposome
1. LIPOSOMES
PRESENTED BY GUIDED BY
PRIYANKA GOSWAMI 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
• COMPOSITION OF LIPOSOME
• MECHANISM
• FACTORS AFFECTING
• ADVANTAGES AND DISADVANTAGE
• CLASSIFICATION
• METHOD OF PREPARATION
• EVALUATION
• APPLICATION
• MARKETED PRODUCT
• UNDER CLINICAL TRIAL PRODUCT
• REFERENCE
Faculty of pharmaceutical science, ADTU 2
3. INTRODUCTION
• Liposome are spherical vesicle having in which aqueous core is entirely enclosed by one
or more phospholipid bilayers.
• Liposome is derived from the Greek word where lipo = fatty constitution and soma =
structure.
• Liposome were first discovered in the early 1965 by Alec D. Bangham.
• Liposome are relatively small it ranges from 50 nm to several micrometers in diameter.
Faculty of pharmaceutical science, ADTU 3
4. COMPOSITION OF LIPOSOME
• Phospholipid: Phospholipids are the major structural components of biological membrane such
as the cell membrane. Phospholipid consist hydrophobic tail and hydrophilic head or polar head.
Hence both hydrophilic drugs can be encapsulated in the aqueous phase and hydrophobic drug
molecule can be incorporated in the lipid layer.
Hydrophobic tail consist of 2 fatty acid chain
containing 10-20 carbon atoms and 0.6 double
bond in each chain. Hydrophillic head consist
phosphoric acid bound to water soluble molecule.
Faculty of pharmaceutical science, ADTU 4
5. COMPOSITION OF LIPOSOME
• Cholesterol: cholesterol does not by form bilayer structure, but can be incorporated into
phospholipid membrane in vey high concentration. It improve the fluidity of the bilayer
membrane and reduce the permeability of bilayer membrane in the presence of
biological fluids such as blood/plasma. Cholesterol appears to reduce the interaction
with blood proteins.
Faculty of pharmaceutical science, ADTU 5
6. ADVANTAGES
• Suitable for delivery of hydrophobic e.g amphotericin B, hydrophilic e.g cytrabine and
amphipatic drus agents.
• Liposome increases efficacy and therapeutic index of drug (actinomycin-D)
• Liposome increase stability via encapsulation
• Suitable for controlled release
• Suitable to give localized action in particular tissue
• Suitable to administer via various routes
• Liposomes help to reduce the exposure of sensitive tissue to toxic drug.
Faculty of pharmaceutical science, ADTU 6
7. DISADVANTAGES
• Once administrated, liposome can not be removed.
• Possibility of dumping, due to faulty administration.
• Leakage of encapsulated drug during storage.
• Low solubility
• Production cost is high.
Faculty of pharmaceutical science, ADTU 7
8. MECHANISM OF FORMATION OF LIPOSOME
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.
Faculty of pharmaceutical science, ADTU 8
9. CLASSIFICATION
BASED ON STRUCTURAL PARAMETERS
• MLV: multilamellar large vsicles .0.5 µm. They have several bilayer
• OLV: Oligolamellar vesicles 0.1-1µm. Made up of 2-10 bilayer of lipid surrounding a large internal volume.
• UV: Unilamellar vesicles (all size range)
• SUV: Small unilamellar vesicle composed of single lipid bilayer with diameter ranging from 30-70 nm
• MUV: Medium unilamellar vesicle
• LUV: Large unilamellar vesicle > 100 µm
• GUV: Giant unilamellar vesicle >1µm
• MV: Multivesicular vesicle >1µm
Faculty of pharmaceutical science, ADTU 9
10. CLASSIFICATION
BASED ON METHOD OF LIPOSOME PREPARATION
• REV: Single or oligolamellar vesicles made by reverse phase evaporation method
• MLV-REV: Multilamellar vesicle made by reverse phase evaporation method
• SPLV: Stable plurilamellar veicle
• FATMLV: Frozen and thawed MLV
• VET: Vesicle prepared by extraction method
• DRV: Dehydration-rehydration method
Faculty of pharmaceutical science, ADTU 10
11. CLASSIFICATION
BASED ON COMPOSITION AND APPLICATION
• Conventional Liposomes (CL): Neutral or negatively charged phospholipid and cholesterol
• Fusogenic Liposomes (RSVE): Recostituted sendai virus envelopes
• pH sensitive Liposomes: Phospholipid such as PE or DOPE with either CHEMS or OA
• Cationic Liposomes: Cationic lipids with DOPE
• Long Circulatory (stealth) Liposomes (LCL): Liposome that persist for prolong period of time in the blood
stream
• Immuno-Liposomes: : immune liposome have specific antibody on their surface to enhance target site
binding.
Faculty of pharmaceutical science, ADTU 11
12. METHOD OF LIPOSOME PREPARATION
Faculty of pharmaceutical science, ADTU 12
In these processes, the lipids are dissolved in solvents
which are then transfer to round bottom flask. The RBF
containing the mixture is then attached to rotary
evaporator and then it was rotated at 60 rpm until a dry
thin layer is formed after that it is dried in lyophilizer to
remove the last traces of solvent and it is hydrated with
phosphate buffer saline containing the material to be
entrapped and then it was attached to rotary evaporator at
60 rpm or below it was rotated until the layer adhering on
the wall of the RBF is removed and it was kept stand at
room temperature for 2 hr upon hydration the lamella
swells and form myelin figure
HAND-SHAKING MLVs
13. METHOD OF LIPOSOME PREPARATION
NON-SHAKING METHOD
In these method lipid mixed with chloroform: methanol is spread over the conical flask and the
solution is evaporated at room temperature without disturbing by the flow of nitrogen. After
the solution gets dried it is hydrated by water-saturated nitrogen which is passed through the
conical flask until the opacity of dried lipid film disappears. After hydration, the lipid gets
swelled. Then the flask is inclined to one side and 10 to 20 ml of 0.2 M sucrose in distilled water
is added to the side of the flask and then the flask is slowly returned to its original position.
The fluid gently runs over the lipid layer on the bottom of the flask. Then the flask is flushed
with nitrogen and sealed it was then allowed to stand for 2 hr. at room temperature. After
swelling the suspension is centrifuged at 12000 g for 10 min at room temperature
Faculty of pharmaceutical science, ADTU 13
14. METHOD OF LIPOSOME PREPARATION
This method is also known as microfluidization. Here microfluidizer is
used to prepare small MLVs from concentrated lipid dispersion. The
lipid can be introduced into fluidizers, either as a slurry of unhydrated
lipids in organic medium or as a dispersion of large MLVs.
Microfluidizer pumps the fluid at very high pressure through a 5 μm
orifice and then it is forced along defined microchannels, which direct
two streams of fluid to collide together at right angles at a very high
velocity, thereby affecting an efficient transfer of energy. The fluid that is
collected to be recycled through spherical dimension is obtained after a
single pass; the size of the vesicle is reduced to a size 0.1 and 0.2 μm in
diameter.
Faculty of pharmaceutical science, ADTU 14
MICRO-EMULCIFICATION
15. METHOD OF LIPOSOME PREPARATION
This method is carried out either with LUV or
MLV. So initially, in these processes, the
phospholipids are introduced in the buffered
saline solution to form LUV or MLV. After
that, the liposome is passed through
polycarbonate membrane filter which results in
uniform distribution of liposome which is of
about 100 nm in diameter
Faculty of pharmaceutical science, ADTU 15
MEMBRANE EXTRACTION
16. METHOD OF LIPOSOME PREPARATION
BATH SONICATOR:
These processes are generally used for the large volume of dilute lipids which may not be
required to reach the vesicles size. The liposome suspension is kept in a test tube and it
placed in a bath sonicator. Controlling the temperature of the lipid dispersion is usually
easier in this method in contrast to sonication by dispersal directly using the tip. Size of
the liposome is influenced by temperature, composition and concentration, sonication
time and power, the volume of the product
Faculty of pharmaceutical science, ADTU 16
ULTRA-SONICATION
17. METHOD OF LIPOSOME PREPARATION
PROBE SONICATION:
The tip of the sonicator is directly dipped into the liposome dispersion which results in the
local heating so the vessel containing the liposome dispersion must be immersed into the
ice bath. Sonication up to 1 hr. may result in deesterification of more than 5 % lipid. It has
the chances of contaminating the preparation with metal which may lead to degradation
of the lipid. This method is generally used for the suspension which requires high energy
in a small volume
Faculty of pharmaceutical science, ADTU 17
19. METHOD OF LIPOSOME PREPARATION
ETHANOL INJECTION:
In this method, a lipid solution of ethanol is rapidly injected to a vast excess of the buffer
as a result MLVs are immediately formed.
ETHER INJECTION:
A solution of lipids dissolved in diethyl ether or ether and the mixture is slowly injected to
an aqueous solution of the material to be encapsulated at 55 to 65 °C or under reduced
pressure. The subsequent removal of ether under vacuum leads to the formation of
liposomes
Faculty of pharmaceutical science, ADTU 19
20. Fig. Ethanol injection and ether injection
Faculty of pharmaceutical science, ADTU 20
METHOD OF LIPOSOME PREPARATION
21. METHOD OF LIPOSOME PREPARATION
DOUBLE EMULSION:
In this method the active ingredient is mixed to the aqueous phase (w1) and then it was mixed
with an organic phase to make a primary emulsion (w1/o) and then the primary emulsion is
mixed with an aqueous phase to make a double emulsion w1/o/w2. The removal of the
solvent leaves microspheres in the aqueous continuous phase, making it possible to collect
them by centrifuging or filtering
REVERSE PHASE EVAPORATION VESICLE:
In this method at first w/o emulsion is prepared by brief sonication. The liposome is
formed when the residual solvent is removed by rotary evaporation under reduced
pressure
Faculty of pharmaceutical science, ADTU 21
22. EVALUTION OF LIPOSOME
• Physical properties:
• Size and its distribution
• Surface charge
• Percent capture
• Lamellarity
• Drug release
• Chemical properties:
• Phospholipid concentration
• Cholesterol analysis
• Stability analysis
Faculty of pharmaceutical science, ADTU 22
23. APPLICATION
• Cancer chemotherapy:
• 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.
• Liposome for topical application:
• Drug like triamcilone, methotrexate, benzocaine, corticosteroids etc. Can be successfully incorporated as topical
liposome.
• Liposome for pulmonary delivery:
• Inhalation devises like nebulizers are use to produce an aerosol of droplets containing liposome.
Faculty of pharmaceutical science, ADTU 23
24. MARKETED PRODUCT
Marketed product Drug used Target diseases company
amphotecTM Amphotericin-B Fungal infection SEQUUS, USA
Depocyt cytrabine Cancer therapy Skye pharm, USA
DaunoXomeTM Daunsolid tumoursorubicin Lung cancer neXstar, USA
Faculty of pharmaceutical science, ADTU 24
25. UNDER CLINICAL TRIAL
drug Target disease status product
nystatin Fungal infection Phase II SEQUUS
Anamycin Kaposi’s sarcoma Phase III Aronex USA
Amikacin Bacterial infection Phase II NeXstar, USA
Faculty of pharmaceutical science, ADTU 25
26. REFERENCE
• N.K. Jain, controlled and novel drug delivery, CBS publisher and distributer, 304-344.
• S.P. Vyas and R.K. Khar, targeted and controlled drug delivery, novel carrier system, CBS publisher, 173-243.
• Liposome:classification,preparationandapplicationswww.Ncbi.Nlm.Gov>articles
• Chauhan T, Arora S, Parashar B, Chandel A, Liposome drug delivery: a review, international journal of
pharmaceutical and chemical sciences, 2012, 1, 1103-1113.
• Rawal G, Sharma T, liposomal drug delivery system: an overview, international journal of pharmaceutical &
biological archives, 2011, 2, 1575-1580.
• Shashi K, Kumar S, Bharat P, A complete review on: liposome, international research journal of pharmacy, 2012, 3, 10-
16.
• Goswami P, Changmai A, Barakoti H, Choudhury A, Dey BK. A brief review on liposomal drug delivery system.
J.Pharm Adv Res, 2018; 1(8): 362-368.
Faculty of pharmaceutical science, ADTU 26