Liposomes:

Formation, preparation, properties and applications

Dr. S.S.Apte

Professor, Univ. College of Pharm. Sci., Kakatiya University, Warangal

Presently:NDDS Divn, Natco Research CentreHyderabad

Liposomal Anthracycline Antibiotics Used in Therapy

Product Drug Marketed By Registration Year

DaunoXome Daunorubicin citrate

NeXstarPharmaceutical

Inc.

EnglandSwedenUSA

1995 r.1995 r.1996 r.

Doxil Doxorubicin SequusPharmaceutical

Inc.

USA 1995

Caelix Doxorubicin 

Schering-Plough Selected EuropeanCountries

1995 r.

Definition of Liposomes

Liposomes are spherical, self closed structures composed of curved lipid bilayers which entrap part of the solvent, in which they freely float, into their interior. They may consist of one or several concentric membranes; their size ranges from 20 nm to several dozens µm, while thickness of the membrane is around 4 nm.

Salient features

Discovered in 1968 by Alec Bangham

Delivery system for hydrophilic, lipophilic, and amphiphilic APIs

Solubilization of lipophilic and amphiphilic APIs

Protection of the API

Reduction of side effects - toxicity of the active

Sustained release

Drug targeting

Low application dose

Classification of Liposomes

SUV = Small Unilamellar Vesicles LUV = Large Unilamellar Vesicles MLV = Multilamellar Vesicles LLC = Lamellar Liquid Crystalline Phase MVV = Multivesicular vesicles

Liposomes are composed of one to several

hundreds concentric membranes

Vesicles

Niosomes (Nonionic surfactants +cholesterol)

liposomes (phospholipids + Cholesterol)

Vesicular delivery systems

Preparation of vesicles:

Film casting via organic solvent

film hydration

ether-ethanol injection

Reverse phase evaporation

Through mixed micellar solution

Mechanical methods

Characterization of vesicles:

Size and size distribution - Dynamic light scattering

Electron microscopy

Coulter counter

Number of lamellae - NMR spectroscopy

small angle X ray scatter

Charge - Microelectrophoresis

Entrapment efficiency - Gel filtration

Capture volume - ultrafiltration

dialysis

protamine aggregation

ultracentrifugation

Release - Dialysis

Liposomal Delivery of Anti-Cancer Agents

Slow Release: reduced peak levels of free drug and prolonged

tumor exposure

Change in Biodistribution: avoiding drug deposition in certain

tissues will reduce tissue-specific toxicities

Tumor Targeting: passive accumulation by enhanced

permeability and retention (EPR) effect

Phospholipids in topical pharmaceutical applications

Drug Effects

Benzoyl peroxide

Flurbiprofen

Diclofenac

Heparin

Clindamycin phosphate

Aciclovir

Menthol & camphor

N,N-diethyl-meta-toluamide (DEET)

Povidone-Iodine

Tamoxifen

Econazol, Miconazol

Glycolic acid

Bethametasone 17-benzoate

improved drug delivery; higher anti-bacterial efficacy

better penetration; improved efficacy in pain treatment

improved drug delivery; higher drug efficacy

improved penetration; higher drug efficacy

sustained release, drug efficacy improvement

enhanced penetration

enhanced penetration, rapid onset of action

controlled release, inhibition of absorption

improved drug delivery & efficacy

improved penetration and drug retention in the skin

drug retention in the skin

controlled release

penetration enhancement