International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.1, No.3, pp 914-917, July-Sept 2009 INFLUENCE OF LIPOSOME COMPOSITION ON PACLITAXEL ENTRAPMENT AND pH SENSITIVITY OF LIPOSOMES Smita Rane 1 *, Bala Prabhakar 2 1 School of Pharmacy and Technology Management, Shirpur Campus, NMIMS University, Shirpur, Maharashtra. 2 School of Pharmacy and Technology Management, NMIMS University, Vile Parle, Bombay, Maharashtra *Email: smita.edu@hotmail.com Abstract: The objective of the present investigation was to study the effect of composition of phospholipids on drug entrapment efficiency and pH sensitivity. In the present study, paclitaxel containing liposomes of different phospholipid compositions were formulated and compared. The formulation composed of Phospholipon 90G/DOPE/CHEMS 8:2:2(D) containing paclitaxel and lipids in the molar ratio of 1:30 (drug: lipid) was found to have good incorporation efficiency(94%). The highest paclitaxel concentration achievable in the liposomal formulation was 1.5 mg/ml. Liposomes with phospholipon 90 G alone couldn’t show pH sensitivity. Formulation B (Phospholipon 90G /DOPE 8:2) released drug at pH 5.5, but was unstable at pH 7.5. On inclusion of CHEMS, liposomes were stabilized at physiological pH, and released paclitaxel at lower pH. Thus including CHEMS into liposomal formulation of paclitaxel, composed of Phospholipon 90 G/DOPE has proved to be the most efficient pH sensitive system with 94 % entrapment efficiency. This formulation showed 96% drug release at pH 5 within 15 min. Keywords : Paclitaxel, Liposomes, pH sensitivity, Entrapment efficiency Introduction: Paclitaxel, the first of a new class of microtubule stabilizing agents, has been hailed by National Cancer Institute (NCI) as the most significant advance in chemotherapy of the past 20-25 years. 1 Due to its low solubility in water, it is clinically administered after dissolving in cremophore EL and ethanol, 2,3 One of the substantial problems associated with this formulation is that the ethanol: Cremophor vehicle is toxic. 4-7 Inclusion of paclitaxel in liposomal formulations has proved to be a good approach to eliminating this vehicle and improving the drug’s antitumor efficacy. pH sensitive liposomes have been suggested as a means to increase intracellular delivery of drugs. These liposomes are stable at physiologic pH (pH 7.4) but undergo destabilization and acquire fusogenic properties under acidic conditions, thus leading to the release of their aqueous contents. pH sensitivity of liposomes may mainly depend on their composition. Different classes of pH sensitive liposomes have been proposed in the literature, based on the mechanism of triggering pH sensitivity. 8 The most commonly established hypothesis involves the blend of phophatidyl ethanolamine and its derivatives with compound containing an acidic group that acts as a stabilizer at neutral pH. 9,12 Contemporary studies describe the use of novel pH sensitive lipids, synthetic fusogenic peptides/proteins either encapsulated or included in the lipid bilayer. 13,15 The objective of the present investigation was to study the effect of composition of phospholipids on drug entrapment efficiency and pH sensitivity. Materials and Methods Paclitaxel was received as a gift sample from Naproid life sciences, Mumbai. Phospholipon 90 G(PL90G) was received as a gift sample from Phospholipid GmbH, Nattermannalle, Germany. Cholesteryl hemisuccinate (CHEMS) was received as a generous gift from Merk Eprova AG Switzerland. Diolyl phosphatidylethanolamime (DOPE) was received as a gift sample from Lipoid GmbH, Germany. HPLC grade