کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1427343 986860 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Optimization of (1,2-diamino-cyclohexane)platinum(II)-loaded polymeric micelles directed to improved tumor targeting and enhanced antitumor activity
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Optimization of (1,2-diamino-cyclohexane)platinum(II)-loaded polymeric micelles directed to improved tumor targeting and enhanced antitumor activity
چکیده انگلیسی

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 nm 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-Luc) 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 121, Issue 3, 28 August 2007, Pages 146–155
نویسندگان
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