Oman Pharmaceutical Products (Gulf), Oman
Title: Formulation of liposomes for oral delivery of phyllanthin and hypophyllanthin
Biography: Thahera Parveen Dandu
Formulation of liposomes in order to enhance the oral bioavailability of phyllanthin and hypophyllanthin with proven anticancer activity. The bioactive lignans, Phyllanthin and hypophyllanthin are formulated in to conventional and PEGylated liposomes using different ratios of DSPC, DSPE-MPEG2000 and cholesterol by film hydration technique. Evaluation of the prepared liposomes was done by the determination of encapsulation efficiencies, particle size analysis, polydispersity index (PDI), zeta potential, TEM analysis, IR studies, DSC studies and powder X-RD analysis. The drug retention in vitro and pharmacokinetic properties in vivo are investigated. A new, simple and sensitive analytical method using HPLC with photodiode array (PDA) detection was developed for the determination of phyllanthin and hypophyllanthin in solvent system and in plasma.Conventional and pegylated liposomes are successfully formulated using film hydration technique with encapsulation efficiencies of 86.47%±0.13% and 83.68±0.22% (phyllanthin), 84.83±0.19% and 81.87±0.54% (hypophyllanthin). The HPLC method was successfully applied for quantification of lignans with recorded LOD and LOQ values of 56.15 ng/mL & 169.99 ng/mL (phyllanthin) and 56.04 ng/mL and 169.82 ng/mL (hypophyllanthin), respectively. From the in vivo pharmacokinetic studies, it was observed that the oral bioavailability of lignans was enhanced as indicated by AUC values of 5265.30±275.52 ng.h/mL (phyllanthin), 15217.60±987.96 ng.h/mL (conventional liposomal phyllanthin), 30810.23±2587.96 ng.h/mL (pegylated liposomal phyllanthin) and 7354.42±578.2 ng.h/mL (hypophyllanthin), 29222.4±1951.8 ng.h/mL (conventional liposomal hypophyllanthin), 58631.87±2515.46 ng.h/mL (pegylated liposomal hypophyllanthin). The developed liposomal formulations of both the lignans, showed extended drug release over 24 h in in vitro drug release studies. Pharmacokinetic studies showed the enhancement of oral bioavailability by several folds for liposomes. The enhanced oral bioavailability of lignan loaded liposomes will be helpful for the production of desired pharmacological activity relatively at a lower dose when compared to their respective free drugs.