title: Synthesis, characterization and anti-cancer activity of Pluronic F68-curcumin conjugate micelles.
abstract: Curcumin (CUR), a nontoxic polyphenol derived from the rhizome of turmeric (Curcuma longa), has been recognized as an anti-cancer and chemo-preventative agent. However, its clinical application for cancer treatment has been greatly limited due to its poor water-solubility and low bioavailability. To tackle this problem, Pluronic F68-CUR (F68-CUR) conjugate micelles, which are amphiphilic copolymers, were designed and synthesized in this study. These highly stable micelles with CUR concentrated in the core were formulated using the solvent evaporation method and were confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Physicochemical characterization of F68-CUR conjugate micelles revealed that high drug loading content (DL%; 0.248 mg CUR/1 mg F68) was achieved, and the average particle size of micelles was 115.2 ± 3.0 nm. Compared with free CUR, a significantly higher cytotoxicity against human breast cancer cell line MDA-MB-231 was observed in F68-CUR conjugate micelles. The IC50value of F68-CUR conjugate micelles was 1.95-fold lower than that of free CUR, indicating that the anti-cancer activity of CUR was significantly improved in the micelles. Furthermore, apoptotic studies demonstrated that F68-CUR conjugate micelles induced more cell apoptosis than that of free CUR. Taken together, these results demonstrate that F68-CUR conjugate micelles are promising to improve the clinical effectiveness of CUR in cancer treatment.
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine , Institute of Chinese Medical Sciences, University of Macau , Macao , P.R. China.
authors.forename: Yuee
authors.initials: Y
authors.lastname: Cai
authors.affiliation: b Department of Pharmacology , School of Medicine, Jinan University , Guangzhou , P.R. China , and.
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Sun
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine , Institute of Chinese Medical Sciences, University of Macau , Macao , P.R. China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Fang
authors.affiliation: c Department of Pediatrics , College of Medicine, University of Florida , Gainesville , FL , USA.
authors.forename: Xiefan
authors.initials: X
authors.lastname: Fang
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine , Institute of Chinese Medical Sciences, University of Macau , Macao , P.R. China.|b Department of Pharmacology , School of Medicine, Jinan University , Guangzhou , P.R. China , and.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine , Institute of Chinese Medical Sciences, University of Macau , Macao , P.R. China.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine , Institute of Chinese Medical Sciences, University of Macau , Macao , P.R. China.
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001682:Biological Availability; D045744:Cell Line, Tumor; D003474:Curcumin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008823:Micelles; D020442:Poloxamer / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D020442:Poloxamer; D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Cancer chemotherapy; Pluronic F68; conjugate micelle; curcumin