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

• Published in: International journal of pharmaceutics 2017-01, Vol.517 (1-2), p.1-7
• Main Authors: Liu, Yan, Luo, Xiao, Xu, Xiaochao, Gao, Nannan, Liu, Xiaohong
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - blood; Antineoplastic Agents, Phytogenic - pharmacokinetics; Bioavailability; Biological Availability; Chromatography, High Pressure Liquid; Drug Carriers - chemistry; Drug Compounding; Drug Design; Drug Stability; Liposomes; Male; Oleanolic acid; Oleanolic Acid - administration & dosage; Oleanolic Acid - blood; Oleanolic Acid - pharmacokinetics; Particle Size; Polyvinylpyrrolidone; Povidone - chemistry; Rats, Sprague-Dawley; Sodium deoxycholate; Solubility; Surface Properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.11.056

[Display omitted] 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.