Journal
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
Volume 24, Issue 8, Pages 986-998Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/09205063.2012.729489
Keywords
diblock polymers; micelles; cytotoxicity; drug delivery
Funding
- National Natural Science Foundation of China [21164007, 51203073]
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A diblock copolymer of monomethoxy-poly(ethylene glycol)-b-poly(L-lactide) (MePEG-PLLA)/brefeldin A (BFA) conjugate was synthesized by the reaction of carboxyl-terminated copolymer MePEG-PLLA with BFA in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The conjugation efficiency was found to be 95%. Its structure was confirmed by H-1 nuclear magnetic resonance and gel permeation chromatography. The MePEG-PLLA/BFA conjugate could self-assemble into micelles in aqueous solutions with a low critical micelle concentration of 1.8x10(3)g/L. Dynamic light scattering and transmission electron microscopy analyses of the MePEG-PLLA/BFA micelles revealed their spherical structure with an average diameter of 120nm. The release profiles of BFA in PBS were measured by high performance liquid chromatography (HPLC), demonstrating that the controlled release of BFA can be gained for long time. The in vitro antitumor activity of the conjugate micelles against human liver carcinoma HepG2 cells was evaluated by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide method, and the results showed that BFA can be released from the conjugate micelles without losing cytotoxicity.
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