Novel freeze-drying method for preparation of α-mangostin dry reconstitute liposomal powder

Abstract

Dry reconstitute liposomal powder of α-mangostin, a xanthone derivative from Garcinia mangostana L. (mangosteen) with potent cytotoxic effect in various cancer cell lines, were developed for the first time by the novel one-step freeze-drying method at room temperature with various molar ratios of phosphatidylcholine to cholesterol. The method was based on utilizing sublimation of volatile solid inert carrier, chlorobutanol hemihydrate, instead of ice in conventional freeze-drying process. The optimum conditions used in sublimation process of chlorobutanol were at temperature 25-30 °C and pressure 1.5-2.0 mBar for 8 hr. The reconstituted liposomal dispersions were multilamellar vesicles with particle size ranging from 649-892 nm and zeta potential of -12 mV. The localization of α-mangostin molecules appeared to be mostly on the surface of liposomes as indicated by drug-liposome binding interaction study using 31P NMR. The entrapment efficiency and loading capacity of α-mangostin in all liposomal formulations were around 80-85% and 4%, respectively. The α-mangostin dry reconstitute liposomal powder prepared by this method were shown to be stable upon storage at 4 °C and 25 °C. The cytotoxicity of α-mangostin liposomes on growth of human lung cancer H460 cells exhibited the ED 50 of much higher than 250 μg/ml as compared to 5.12 μg/ml of pure α-mangostin. © 2012 American Scientific Publishers. All rights reserved.