期刊
AICHE JOURNAL
卷 56, 期 7, 页码 1922-1931出版社
WILEY-BLACKWELL
DOI: 10.1002/aic.12119
关键词
micelle; drug delivery; modelling; cholesterol; oligopeptide
资金
- National Natural Science Foundation of China [20536020, 20776049]
- Guangdong Province Science Foundation [9251064101000009]
- China Scholarship Council
A doxorubicin (DOX) delivery system of pH-sensitive micelles self-assembled from cholesterol conjugated His(5)Arg(10) (HR15-Chol) and His(10)Arg(10) (HR20-Chol) has been described in this article. The amphiphilic molecules have low critical micelle concentrations of 17.8 and 28.2 mu g/ml for HR15-Chol and HR20-Chol, respectively, even at a low pH of 5.0. The pH-sensitive histidine segment of the polypeptide block is insoluble at pH 7.4 but becomes positively charged and soluble via protonation at pH lower than 6.0. The size and zeta potential of DOX-loaded micelles increases with the decrease in pH. Coarse-grained simulations were performed to verify the structure of DOX-loaded micelles and pH sensitivity of HR15/20-Chol. The in vitro DOX release from the micelles is significantly accelerated by decreasing pH from 7.4 to 5.0. Furthermore, DOX release from the micelles is controlled by a Fickian diffusion mechanism. These micelles have great potential applications in delivering hydrophobic anticancer drugs for improved cancer therapy. (C) 2009 American Institute of Chemical Engineers AIChE J, 56: 1922-1931, 2010
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