Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 101, Issue 2, Pages 627-640Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.22798
Keywords
chitosan; polymeric drug delivery system; drug targeting; micelle; cancer chemotherapy
Funding
- Natural Science Foundation of Jiangsu Province [BK2007173]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [200803161017]
- Ministry of Science and Technology, China [2009ZX09310004]
- National Science Foundation of China [81102397]
- Nanjing Welman Institute of Materia Medica
- new foundation of National Basic Research Program of China (973 Program) [2009CB903300]
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Octreotide (OCT) was recently found to have high binding affinity to the positive tumor cells of somatostatin receptors (SSTRs). In this study, octreotidePhepolyethylene glycolstearic acid was first successfully synthesized and used as a targeting molecule for N-octyl-O, N-carboxymethyl chitosan (OCC). Doxorubicin (DOX) was loaded into OCT-modified OCC micelles (DOXOCCOCT). The drug-loaded micelles obtained exhibited spherical shape, small particle sizes, and negative zeta potentials. The cytotoxicity of DOXOCCOCT micelles against MCF-7 cells (SSTRs expressing) was found to significantly increase with the increased amount of OCT modification, whereas no significant difference was observed against WI-38 cells (no SSTRs expressing). Results of flow cytometry, fluorescence microscopy, and confocal laser scanning microscopy confirmed that DOXOCCOCT micelles could remarkably increase the uptake of DOX in MCF-7 cells. All the results indicated that OCCOCT micelles may be a promising intracellular targeting carrier for efficient delivery of antitumor drugs into tumor cells. (C) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:627640, 2012
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