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      1. Author :
        Cabral, Horacio; Nishiyama, Nobuhiro; Kataoka, Kazunori
      2. Title :
      3. Type :
        Journal Article
      4. Year :
      5. Publication :
        Journal of controlled release: official journal of the Controlled Release Society
      6. Products :
      7. Volume :
      8. Issue :
      9. Page Numbers :
      10. Research Area :
      11. Keywords :
        Animals; Antineoplastic Agents; Bioware; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Female; Hela Cells; HeLa-luc; Humans; Mice; Mice, SCID; Micelles; Neoplasms; Organoplatinum Compounds; Platinum; Polymers; Xenograft Model Antitumor Assays
      12. Abstract :
        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.
      13. URL :
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
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