期刊
JOURNAL OF CONTROLLED RELEASE
卷 121, 期 3, 页码 146-155出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2007.05.024
关键词
polymeric micelles; DACHPt; oxaliplatin; biodistribution; antitumor activity
Polymeric micelles are promising nanocarriers, which might enhance the efficacy of antitumor drugs. Herein, polymeric micelles incorporating dichloro(1,2-diamino-cyclohexane)platinum(II) (DACHPt), the oxaliplatin parent complex, were prepared through the polymer-metal complex formation of DACHPt with poly(ethylene glycol)-b-poly(glutamic acid) [PEG-b-P(Glu)] block copolymer having different lengths of the poly (glutamic acid) block [p(Glu): 20, 40, and 70 U]. The resulting micelles were studied with the aim of optimizing the system's biological performance. DACHPt-loaded micelles (DACHPt/m) were approximately 40 ran in diameter and had a narrow size distribution. In vivo biodistribution and antitumor activity experiments (CDF1 mice bearing the murine colon adenocarcinoma C-26 inoculated subcutaneously) showed 20-fold greater accumulation of DACHPt/m at the tumor site than free oxaliplatin to achieve substantially higher antitumor efficacy. Moreover, the micelles prepared from PEG-b-P(Glu) with 20 U of P(Glu) exhibited the lowest non-specific accumulation in the liver and spleen to critically reduce non-specific accumulation, resulting in higher specificity to solid tumors. The antitumor effect of DACHPt/m was also evaluated on multiple metastases generated from intraperitoneally injected bioluminescent HeLa (HeLa-Lue) cells. The in vivo bioluminescent data indicated that DACHPt/m decreased the signal 10-to 50-fold compared to the control indicating a very strong antitumor activity. These results suggest that DACHPt/m could be an outstanding drug delivery system for oxaliplatin in the treatment of solid tumors. (C) 2007 Elsevier B.V All rights reserved.
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