Liposomal drug delivery involves encapsulating drugs within liposomes, which are spherical vesicles composed of phospholipid bilayers, to improve drug targeting and reduce toxicity. Liposomes can be classified based on lamellarity, size, and method of preparation. Drugs are encapsulated within the aqueous interior or phospholipid bilayer of liposomes. Liposomes protect drugs, control drug release, and can be targeted to specific tissues. Applications include cancer therapy, antimicrobial delivery, ophthalmic delivery, and topical delivery to improve treatment.

1. LIPOSOMAL DRUG
DELIVERY
Presented by : Alexa Jacob
M.pharm 2nd sem
Dept. of Pharmaceutics
St.Joseph’s College of Pharmacy,Cherthala
Alappuzha,Kerala
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2. CONTENTS
 Definition
 Structural Components
 Classification
 Method Of Preparation
 Evaluation
 Applications 2

3. LIPOSOMES
 A Liposome is a spherical vesicle with a membrane composed of a phospholipid & cholesterol bilayer.
 Liposomes can be produced from cholesterols, non toxic surfactants,sphingolipids,glycolipids,long chain fatty
acids & even membrane proteins.
 Liposomes are the drug carrier loaded with great variety of molecules such as small drug molecules, proteins,
nucleotides & even plasmids.
 Liposomes can be made in a particular size range that makes them viable targets for natural macrophage
phagocytosis.
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4. STRUCTURAL COMPONENTS
 The main components of liposomes are :-
 1. Phospholipids
 2. Cholesterol
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5. 1) PHOSPHOLIPIDS
 Phospholipids are the major structural components of biological membranes such as the cell membrane.
Two types of Phospholipids
(along with their hydrolysis
products)
Phosphoglycerides
Sphingolipids
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6.  Each phospholipid molecule has 3 major parts, 1 head & 2 tails. Head is made from 3 molecular components:
choline , phosphate & glycerol which is hydrophilic. Each tail with a long chain which are hydrophobic.
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7. Commonly Used Phospholipids
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8. 2) CHOLESTROL
 Cholesterol is generally used steroid in the formulation of liposomes.
 It improves the fluidity of the bilayer membrane and reduces the permeability of bilayer membrane in the
presence of biological fluids such as blood / plasma.
 Cholesterol appers to reduce the interactions with blood proteins.
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9. CLASSIFICATION
 Liposomes can be classified based on three different criteria
 Based on structural parameters
 Based on method of preparation
 Based on composition and applications
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12. 12

13. NOVEL LIPOSOMES
Transferosomes
Archaeosomes
Proteosomes
Virosomes
Ethosomes
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14. 14

15. I.MECHANICAL DISPERSION
 Hand-shaken Multi-lamellar vesicles :-
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16.  Non-Shaking Vesicles :-
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17.  Microemulsification Liposomes :-
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18.  Sonicated Uni-lamellar Vesicles :-
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19. II.SOLVENT DISPERSION
 Ethanol Injection :-
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20.  Ether Injection :-
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21.  Reverse Phase Evaporation Vesicles :-
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22. III.DETERGENT SOLUBILIZATION
 Their shape & size depends on the chemical nature of detergent , the concentration & other lipids involved.
 The concentration of detergent in water at which micelles just start to form is known as critical micelle
concentration. 22

23.  A three stage model of interaction for detergents with lipid bilayers:
 Stage1: At low concentration detergents equilibrates between vesicular lipid and water phase.
 Stage2: After reaching a critical detergent concentration, membrane structure tends to unstable and
transforms gradually in to micelles.
 Stage3: All lipid exists in mixed micelle form.
 Some methods are applied for removal of detergent and transition of mixed micelles to concentric bilayered
form.
 DIALYSIS:
 The molecules of detergent are removed from mixed micelle by dialysis by lowering the concentration of
detergent in bulk aqueous phase.
 eg: sodium cholate,octylglucoside.
 COLUMN CHROMATOGRAPHY:
 Removal of detergent is achieved by by passing the dispersion over a sephadexg-25 column pre-saturated with
constitutive lipids and pre-equilibrated with hydrating buffer.
 eg: deoxycholate. 23

24. EVALUATION
I.PHYSICAL PROPERTIES
1) Particle size:-
 Microscopic method
 Light microscopy has been utilized to examine the gross size distribution of large vesicles produced from single
chain amphiphiles.
 Laser light scattering
 Proton correlation spectroscopy is the analysis of time dependence of intensity fluctuation in scattered laser
light due to the Brownian motion of particles in solution/suspension.
 Translational diffusion coefficient can be measured here to determine the mean hydrodynamic radius (Rh) of
the particles using stokes-Einstein equation
 Gel permeation
 Exclusion chromatography on large pure gels enable to separate small uni-lamellar vesicles from radial multi-
lamellar vesicles.
D = KT
6πηRh
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25. 2) Surface Charge:-
 Free-flow electrophoresis on a cellulose acetate plate in a sodium borate buffer pH 8.8 & Zeta potential
measurement can also be done.
 The samples are applied to plate & electrophoresis is carried out at 4˚C on a flat bed apparatus for 30 min.
 The plate is dried and phospholipids are visualised by the molybdenum blue reagent
 The surface charge can be calculated by estimating the mobility of the liposomal dispersion in a suitable
buffer.
3) Percent Capture (Entrapment) :-
 This can be determined by ‘PROTAMINE AGGREGATE’ & ‘MINICOLUMN CENTRIFUGATION method .
 In Mini-column centrifugation , the hydrated gel is filled in a barrel of 1ml syringe.
 This barrel is rested in a centrifuge tube spun at 2000rpm for 3 min to remove excess saline solution from gel.
 After centrifugation , gel column is dried.
 Liposome suspension is added dropwise to top of gel bed, & column is spun at 2000rpm for 3min to expel void
volumes containing liposomes into centrifuge tube.
 The elute is then removed & set aside for assay.
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26. 4) Lamellarity :-
 The average number of bilayers present in liposome can be found by Freeze electron microscopy & P NMR
method.
5) Phase Behaviour:-
 Liposomes at transition temperature undergo reversible phase transition i.e the polar head groups in gel state
become disordered to form the liquid crystalline state which can be determined by DSC.
 The phase transition temperature (Tc) is a function of phospholipid content of bilayers.
 Tc can give good clues regarding liposomal stability , permeability or whether the drug is entrapped in bilayers
or in aqueous compartments.
6) Drug Release :-
 The mechanism of drug release from liposome can be assessed by the use of a well calibrated in-vitro diffusion
cell.
 The rate of drug release from the liposomes can be determined by in vitro assays which helps to predict the
pharmacokinetics and bioavailability of the drug.
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27. II.CHEMICAL PROPERTIES
7) Quantitative determination of phospholipids :-
Barlett Assay
 (i) Initially the phosphorous present in the lipid bilayer of the sample is hydrolyzed to inorganic phosphate.
 (ii) Then ammonium molybdate is added to convert inorganic phosphate to phosphomolybdic acid(PMA).
 (iii) The sample is then treated with aminonaphthylsulphonic acid to quantitatively reduce the PMA to a blue-
coloured compound.
 (iv) The intensity of the blue colour produced can be measured by spectrophotometric means and the value is
plotted on the standard curve to obtain the content of phospholipids
8) Quantitative determination of cholesterol :-
 The sample is reacted with a reagent (containing ferric perchlorate, ethyl acetate and H₂SO₄) and the
absorbance of purple coloured complex is measured at 610 nm.
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28. APPLICATIONS
1) Liposomes in cancer therapy :
 High tumour targeting potential
 Eg : DaunosomeTM consist of daunorubicin incorporated into an SUV with a diameter of 40-50nm & composed of
DSPC and cholesterol.
 This composition is supplied as a ready-to-use aqueous liposome.
2) Liposomes in delivery of anti-microbial agents :
 Liposomes are used in treatment of bacterial,fungal,viral & parasitic diseases.
 Liposomes can be used for passive delivery of immunomodulators to macrophages , which brings about non-
specific resistance to infections.
 Eg : AmbisomeTM is a liposomal form that consists of SUV’s composed of hydrogenated PC , distearoyl
phosphatidyl glycerol & cholesterol stored as a lyophilised powder
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29. 3) Liposomes in ophthalmic delivery :
 The efficacy of liposomes in ophthalmic therapy depends on the drug encapsulation efficiency , size & charge
of vesicles, distribution of drug in liposomes, residence time of liposomes in conjuctival sac & affinity of
liposomes to the cornea.
 Eg : Entrapping idoxuridine in liposomes was more effective than free drug in treatment of acute & chronic
herpetic keratitis
4) Liposomes as carrier of drug in oral treatment :
(a) Arthritis :
 Eg : Steroids ( eg: cortisol palmitate) can be entrapped into large multi-lamellar liposomes composed of
dipalmitoyl phosphatidyl choline & phosphatidic acid.
(b) Diabetes :
 Eg : Potential drug delivery system for oral delivery of insulin 29

30. 5) Liposomes as Vaccine adjuvants :
 Enhances potential of both cell mediated & humoral mediated immunity.
 Liposomal immunoadjuvants act by slowly releasing encapsulated antigens on intramuscular injection & also by
passively accumulating within regional lymph nodes.
 Liposomal vaccines are prepared by associating microbes, soluble antigens,cytokines or DNA with liposomes.
 Eg: A liposomal based hepatitis A vaccine (Epaxal) contains formalin inactivated hepatitis A virus particles attached to
phospholipid vesicles together with influenza virus hemaglutinin.
6) Protection against enzyme degradation of drugs
 Liposomes are used to protect the entrapped drug against enzymatic degradation while in circulation.
 The basis is that the lipids used in their formulation are not susceptible to enzymatic degradation; the entrapped
drug is thus protected while the lipid vesicles are in circulation in the extracellular fluid. 30

31. 7) Drug targeting :-
 The approach for drug targeting via liposomes involves the use of ligands (e.g., antibodies, sugar residues,
apoproteins or hormones),which are tagged on the lipid vesicles.
 The ligand recognises specific receptor sites and, thus, causes the lipid vesicles to concentrate at such target
sites.
 By this approach the otherwise preferential distribution of liposomes into the reticuloendeothelial system RES
(liver, spleen and bone marrow) is minimized.
 Examples include anticancer, antiinfection and anti-inflammatory drugs
8) Topical drug delivery :-
 The application of liposomes on the skin surface has been proven to be effective in drug delivery into the skin.
 Liposomes increase the permeability of skin for various entrapped drugs and at the same time diminish the
side effect of these drugs.
 Examples include anaesthetics, corticosteroids. 31

32. REFERENCE
 Controlled & Novel Drug delivery by N.K Jain ; Pg no : 304-326
 Textbook of industrial Pharmacy by Shobha Rani R Hiremath ; Pg no : 97-110
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33. THANKYOU…
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