title: Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo.
abstract: The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA) to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs) were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 μm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger-Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
authors.forename: Zhongbing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xiong
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
authors.forename: Xiaoduan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D004655:Emulsions; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D009828:Oleanolic Acid / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010316:Particle Size; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012995:Solubility; D055672:Static Electricity
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004655:Emulsions; D008081:Liposomes; D009828:Oleanolic Acid
keywords: cancer therapy; controlled release; multivesicular liposomes; murine hepatocellular carcinoma; oleanolic acid