title: 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.
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No.103 Wenhua Road, Shenyang 110016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Materia Medica Chinese Academy of Sciences, No. 501 Haike Road, Shanghai 201210, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No.103 Wenhua Road, Shenyang 110016, China.
authors.forename: Xiaochao
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No.103 Wenhua Road, Shenyang 110016, China. Electronic address: lvj221@163.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D015195:Drug Design; D004355:Drug Stability; D008081:Liposomes; D008297:Male; D009828:Oleanolic Acid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D010316:Particle Size; D011205:Povidone / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008081:Liposomes; D009828:Oleanolic Acid; D011205:Povidone
keywords: Bioavailability; Liposomes; Oleanolic acid; Polyvinylpyrrolidone; Sodium deoxycholate