Preparation, characterization and in vivo pharmacokinetic study of PVP-modified oleanolic acid liposomes

Abstract

The primary purpose of the present study was to design and optimize a liposomal formulation of the poorly water-soluble drug oleanolic acid (OA) to improve its oral bioavailability, and prolong the duration of therapeutic drug level. Liposomes containing a soybean lecithin and cholesterol lipid bilayer, a protective hydrophilic polyvinylpyrrolidone-K30 (PVP-K30) coating, and a protective bile salt, sodium deoxycholate, were prepared by a thin-film dispersion method coupled with sonication. Several properties of the PVP-modified OA liposomes (PVPOALs), including surface morphology, particle size, zeta potential and entrapment efficiency were extensively characterized. The pharmacokinetic parameters of PVPOALs in rats were determined by UPLC–MS/MS following oral administration. The results of the characterization studies demonstrated that PVPOALs were spherical particles with an average particle size of 179.4nm and a zeta potential of −28.8mV. The drug encapsulation efficiency was more than 90%. After freeze-drying, the prepared liposomes possessed high entrapment efficiency of more than 90%. The mean particle size was 194.8nm, and the zeta potential was about −30.9mV. Furthermore, as compared to the commercial tablets, the liposomal formulation enhanced the maximum plasma concentration (Cmax) of OA by 6.90-fold in rat plasma. The relative bioavailability of PVP-modified liposomes was 607.9%. The research work in the paper suggests that PVP-modified liposomes could serve as a practical oral preparation for OA in future cancer therapy.