title: TPGS-g-PLGA/Pluronic F68 mixed micelles for tanshinone IIA delivery in cancer therapy.
abstract: Tanshinone IIA (TAN) has few clinical applications for anti-cancer therapy mainly due to its high lipophicity, low cellular uptake, and poor bioavailability. To improve the anti-cancer effect and bioavailability of TAN, we developed a mixed micelle system constituted with D-α-tocopheryl polyethylene glycol succinate-graft-poly(D,L-lactide-co-glycolide) (TPGS-g-PLGA) copolymer and Pluronic F68. TAN was encapsulated in the TPGS-g-PLGA/Pluronic F68 mixed micelles by using the thin film hydration technology optimized by the central composite design/response surface method (CCD/RSM). TAN-loaded mixed micelles were highly stable in the presence or absence of bovine serum albumin (BSA) and achieved sustained drug release in vitro. Compared with free TAN, TAN mixed micelles had higher cytotoxicity and pro-apoptotic effects against human hepatocellular carcinoma HepG2 cells. The significant enhancement on pro-apoptosis by TAN micelles was evidenced by increased chromosome condensation, mitochondria membrane potential loss, cell apoptosis, and cleavages of caspase-3 and PARP. Furthermore, pharmacokinetic studies revealed that TAN mixed micelles significantly prolonged the circulation time and improved bioavailability of TAN in rats. These results demonstrated that TAN-loaded TPGS-g-PLGA/F68 mixed micelles are an effective strategy to deliver TAN for cancer therapy.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pediatrics, College of Medicine, University of FL, Gainesville, FL 32610, USA.
authors.forename: Xiefan
authors.initials: X
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Demin
authors.initials: D
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China. Electronic address: ytwang@umac.mo.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China. Electronic address: mwchen@umac.mo.
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
mesh_terms: D045784:Abietanes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008823:Micelles; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; C021751:tanshinone; D020442:Poloxamer; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D011092:Polyethylene Glycols; C014225:tocophersolan
keywords: Apoptosis; Cancer therapy; Mixed micelles; Pluronic F68; TPGS; Tanshinone IIA