These vesicles can encapsulate water-soluble drugs in their aqueous spaces and lipid soluble drug within the membrane itself.
The unique property of liposomes, namely their versatile, biodegradable, hypoallergenic nature, along with their similarity to biological membranes are the important factors in the continued efforts to develop liposomal drug delivery froms.
Structurally, liposomes are bilayered vesicles in which an aqueous volume is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids .
In order to understand why liposomes are formed when phospholipids are hydrated, it requires a basic understanding of physiochemical features of phospholipids.
Phospholipids are amphipathic molecules (having affinity for both aqueous and polar moieties) as they have a hydrophobic tail is composed of two fatty acids containing 10-24 carbon atoms and 0-6 double bonds in each chain.
Lipid is solublised in organic solvent, drug to be entrapped is solubilise in aqueous solvent, the lipid phase is hydrated at high speed stirring due to affinity of aqueous phase to polar head it is entrapped in lipid vesicles.
e.g. Lipid film hydration, Micro-emulsification ( Microfluidizer ), Sonication, Dried reconstituted vesicle
in this method, lipids are first dissolved in organic solvent, which then brought in to contact with aqueous phase containing material which is to be entrapped in liposome under rapid dilution and rapid evaporation of organic solvent.
Detergent removal methods
Physical Characterization Surface charge Free-flow electrophoresis Electrical surface potential and surface pH Zetapotential measurements & pH sensitive probes Percent of free drug/ percent capture Drug release Diffusion cell/ dialysis Parameter Characterization method Vesicle shape and surface morphology Mean vesicle size and size distribution Dynamic light scattering, zetasizer, Photon correlation spectroscopy, laser light scattering, gel permeation and gel exclusion Minicolumn centrifugation, ion-exchange chromatography, radiolabelling Transmission electron microscopy, Freeze-fracture electron microscopy
Phopholipid peroxidation UV absorbance, Iodometric and GLC Phospholipid hydrolysis, Cholesterol auto-oxidation HPLC and TLC Osmolarity Parameter Characterization method Phospholipid concentration Cholesterol concentration Cholesterol oxidase assay and HPLC Osmometer Barlett assay, stewart assay, HPLC Chemical Characterization
Biological Characterization Animal toxicity Monitoring survival rates, histology and pathology Parameter Characterization method Sterility Pyrogenicity Limulus Amebocyte Lysate (LAL) test Aerobic or anaerobic cultures
Once liposomes are formed, they behave similar to the other colloidal particles suspended in water.
Neutral particles tend to aggregate or flocculate and sediment with increase in size on storage. Adding charged lipids such as stearyl amine, diactyl phosphate and phosphatidyl serine can control the aggregation.
The addition of charged lipids causes repulsion and prevents major changes in the overall size of liposomes.
Phospholipids, especially those derived from natural sources, are subject to two major degradative reaction :
A. Lipid peroxidation : most phospolipid liposomes contain unsaturated acyl chains as part of their molecular structure and susceptible to oxidative degradation. It can be minimized by the use of animal derived lipids like egg PC, which has less saturated lipids, use of light resistant containers, use of antioxidants are useful in minimizing oxidation.
Cancer Transdermal Methotrexate Meningococal, staphylococcal Pulmonary delivery Penicillin G Glucoma, Conjectivitis Ocular delivery Adrenaline Rheumatoid arthritis Oral delivery Ibuprofen ulcer on mucous surface with pain Transdermal Benzocain Asthma Pulmonary delivery Salbutamol Targeted Diseases Route of administration Drug
Britannia Pharm, UK Expanding lung diseases in babies Dry protein free powder of DPPC-PG ALECTM The liposome company, USA Systemic inflammatory diseases Prostaglandin-E1 VENTUSTM SEQUUS, USA fungal infections, Leishmaniasis Amphotericin-B AmphotecTM NeXstar, USA Kaposi’s sarcoma, breast & lung cancer Daunorubicin DaunoXomeTM SEQUUS, USA Kaposi’s sarcoma Doxorubicin DoxilTM or CaelyxTM Company Target diseases Drug used Marketed product
Swiss serum & vaccine institute, Switzerland Hepatitis A Inactivated hepatitis-A Virions Epaxal –Berna Vaccine Vineland lab, USA Chicken pox Killed avian retrovirus Avian retrovirus vaccine Novavax, USA Smallpox Smallpox vaccine Novasome® Skye Pharm, USA Cancer therapy Cytarabine Depocyt Ozone, USA Asthma Terbutaline sulphate Topex-Br Company Target diseases Drug used Marketed product
Liposomes are one of the unique drug delivery system, which can be of potential use in controlling and targeting drug delivery.
Liposomes are administrated orally, parenterally and topically as well as used in cosmetic and hair technologies, sustained release formulations, diagnostic purpose and as good carriers in gene delivery.
Nowadays liposomes are used as versatile carriers for targeted delivery of drug.