Cis-diamminedichloroplatinum delivery system using poly (lactic acid).

概要

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Cis-diamminedichloroplatinum(CDDP)-contain-ing poly(lactic acid)microspheres(CDDP-MS)with an average diameter of 100 μm, prepared by the oil in oil emulsion method, released 60% of CDDP in Tris buffer within 24 hours. To improve the burst effect of the CDDP-MS, we prepared CDDP-containing poly(D, L-lactic acid) beads(CDDP-B)with a diameter of 2 mm. The CDDP-B showed a 2 phase releasing pattern. The first release was observed within 3 days and 40% of CDDP disappeared, while the second release was seen after 20 days and all of the CDDP disappeared until the day 30. When the CDDP-B was implanted in the femoral muscles of rabbits, peritoneal cavity of mice, and subcutaneous tissues of mice, CDDP was released almost continuously from the CDDP-B and disappeared within 2 to 3 weeks. CDDP was detected in serum for up to 3 weeks, when the CDDP-B was implanted in the peritoneal cavity, indicating slow release of CDDP from the CDDP-B. Histologically, the muscles which had been in contact with the CDDP-B, accompanied inflamma-tory cells and a small area of the necrosed tissue until 5 days and again at the day 14, but they disappeared at the day 7 and at the day 21. This histological change seens to be related to the 2 phase releasing pattern of CDDP from the CDDP-B in vitro.
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