Abstract
a-Mangostin is an oxygenated heterocyclic xanthone with remarkable pharmacological properties, but poor aqueous solubility and low oral bioavailability hinder its therapeutic application. This study sought to improve the compound's solubility and study the mechanism underlying solubility enhancement. Solid dispersions of a-mangostin were prepared in polyvinylpyrrolidone (PVP) by solvent evaporation method and showed substantial enhancement of a-mangostin's solubility from 0.2 +/- 0.2 mu g/mL to 2743 +/- 11 mu g/mL. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated interaction between a-mangostin and PVP. Transmission electron microscopy and dynamic light scattering showed self-assembly of round anionic nanomicelles with particle size in the range 99127 nm. Powder X-ray diffraction indicated conversion of a-mangostin from crystalline into amorphous state, and scanning electron microscopy showed the presence of highly porous powder. Studies using the fluorescent probe pyrene showed that the critical micellar concentration is about 77.4 +/- 4 mu g/mL. Cellular uptake of nanomicelles was found to be mediated via endocytosis and indicated intracellular delivery of a-mangostin associated with potent cytotoxicity (median inhibitory concentration of 8.9 +/- 0.2 mu g/mL). Improved solubility, self-assembly of nanomicelles, and intracellular delivery through endocytosis may enhance the pharmacological properties of a-mangostin, particularly antitumor efficacy. (C) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:815825, 2012