TY - JOUR
T1 - Evaluation in vitro and in vivo of curcumin-loaded mPEG-PLA/TPGS mixed micelles for oral administration
AU - Duan, Yuwei
AU - Zhang, Baomei
AU - Chu, Lianjun
AU - Tong, Henry H.Y.
AU - Liu, Weidong
AU - Zhai, Guangxi
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Curcumin
KW - D-α-tocopherol polyethylene glycol 1000 succinate
KW - Methoxy poly(ethylene glycol)-poly(lactide)
KW - Micelle
UR - http://www.scopus.com/inward/record.url?scp=84957680252&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2016.01.017
DO - 10.1016/j.colsurfb.2016.01.017
M3 - Article
C2 - 26874910
AN - SCOPUS:84957680252
SN - 0927-7765
VL - 141
SP - 345
EP - 354
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
ER -