Formulation and Evaluation of pH Sensitive Long Circulating Liposomes for Anticancer Drug Delivery

Abstract

In this work lipophilic antitumor drug Paclitaxel was incorporated in long circulating pH newlinesensitive liposomes. Liposomes were made of diolylphosphatidylethanolamine (DOPE) : newlinecholesteryl-hemisuccinate(CHEMS): phospha-tidylcholine (PC) 4:6:4 molar ratio, at newline1:23 drug :lipid ratio using chloroform as a solvent. This formula was optimized using newlineBox- Behnken Design. Liposomes were made long circulating but without affecting pH newlinesensitivity by including PEG2000 derivative of CHEMS and evaluated for drug newlineincorporation efficiency, drug release at acidic pH and Physiologic pH, liposomal size, newlinemorphology, zeta potential, stability and in-vivo tumor growth inhibition. In vivo studies newlinewere carried out in a MX1 Human Breast Xenograft model. newlinePaclitaxel is poorly soluble in aqueous medium, and is currently formulated in a vehicle newlinecomposed of 1:1 blend of Cremophor EL and ethanol which is diluted with 5-20 fold in newlinenormal saline or dextrose solution (5%) for administration. One of the substantial newlineproblems associated with this formulation is that the ethanol: Cremophor vehicle is toxic. newlineThe primary goal of formulation development for Paclitaxel is to eliminate the newlineCremophor vehicle and also to provide the possibility of improving the efficacy of newlinePaclitaxel based anticancer therapy. newline