title: Evaluation in vitro and in vivo of curcumin-loaded mPEG-PLA/TPGS mixed micelles for oral administration.
abstract: The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR-MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0 nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP-TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP-TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR-MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75 mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR-MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG-PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors.forename: Baomei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: College of Medicine and Nursing, Dezhou University, Dezhou 253023, China.
authors.forename: Lianjun
authors.initials: L
authors.lastname: Chu
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao, China.
authors.forename: Henry Hy
authors.initials: HH
authors.lastname: Tong
authors.affiliation: Department of Pharmacy, Linyi People's Hospital Affiliated to Shandong University, Linyi 276003, China. Electronic address: 1393170563@qq.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China. Electronic address: professorgxzhai@aliyun.com.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D065546:Drug Liberation; D041981:Gastrointestinal Tract / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017208:Rats, Wistar; D015203:Reproducibility of Results; D014810:Vitamin E / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D014810:Vitamin E; D011092:Polyethylene Glycols; D003474:Curcumin; C014225:tocophersolan
keywords: Curcumin; D-α-tocopherol polyethylene glycol 1000 succinate; Methoxy poly(ethylene glycol)-poly(lactide); Micelle