文献类型：期刊文献

英文题名：Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia

作者：Gong, Feirong[1];Chen, Dan[2];Teng, Xin[1];Ge, Junhua[3];Ning, Xianfeng[3];Shen, Ya-ling[2];Li, Jian[3];Wang, Shanfeng[4]

机构：[1]East China Univ Sci & Technol, Sch Mat Sci & Engn, Minist Educ, Key Lab Ultrafine Mat, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Collaborat Innovat Ctr Biomfg Technol, Sch Biotechnol, Shanghai 200237, Peoples R China;[3]Qingdao Univ, Affiliated Hosp, Dept Cardiol, Qingdao 266003, Peoples R China;[4]Univ Tennessee, Dept Mat Sci & Engn, Knoxville, TN 37996 USA

年份：2017

卷号：14

期号：8

起止页码：2585

外文期刊名：MOLECULAR PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000407405300012)】；

基金：The authors thank the financial support from the National Science & Technology Major Projects (China) for Major New Drugs Innovation & Development (No. 2014-ZX09301306-006).

语种：英文

外文关键词：curcumin; polymer micelles; blood-stable; antitumor

摘要：Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampetecr its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded" copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-b/ockpoly(epsilon-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbony1)-L-phenyldianine end-capped mPEG-PCL (mPEG PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague Dawley rats also Showed higher uptake and slower elimination of curctunin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumiri:loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.