Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1996 Apr;87(4):412–417. doi: 10.1111/j.1349-7006.1996.tb00238.x

Improvement of Intraperitoneal Chemotherapy for Rat Ovarian Cancer Using Cisplatin‐containing Microspheres

Seisuke Kumagai 1, Toru Sugiyama 1, Takashi Nishida 1, Kimio Ushijima 1, Michiaki Yakushiji 1
PMCID: PMC5921101  PMID: 8641974

Abstract

Microspheres consisting of L‐lactic acid and glycolic acid copolymer containing cisplatin (CDDP‐PLGA) were developed to improve the delivery of cisplatin. We evaluated the effects of intraperitoneal administration of cisplatin prepared as CDDP‐PLGA in rats with ovarian cancer. The toxicity, platinum distribution, and therapeutic effects of CDDP‐PLGA were evaluated as compared with those in the case of cisplatin aqueous solution. The LD50 of CDDP‐PLGA was almost four‐fold higher than that of cisplatin aqueous solution. CDDP‐PLGA released cisplatin slowly and achieved a higher concentration in the peritoneal cavity and in peritoneal tumors for prolonged periods, while the tissue concentration of cisplatin was reduced elsewhere in the body, as compared with the case of cisplatin aqueous solution. The survival of rats with peritoneal carcinomatosis was increased by this delivery system relative to cisplatin aqueous solution. CDDP‐PLGA thus allows a higher dose to be given without increasing systemic toxicity, enhancing the therapeutic effect of cisplatin.

Keywords: Drug delivery system, CDDP‐PLGA, Intraperitoneal administration, Ovarian cancer, Rat

Full Text

The Full Text of this article is available as a PDF (330.5 KB).

REFERENCES

  • 1. ) Gregoriades , G.Targeting of drug . Nature , 265 , 407 – 411 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Mizushima , Y. , Shoji , Y. , Saotome , T. , Yanagawa , A. and Nakagawa , T.Current problems and future perspectives in drug delivery systems (DDS) for cancer therapy . Jpn. J. Cancer Chemother. , 15 , 1077 – 1082 ( 1988. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 3. ) Taguchi , T.Targeting therapy for cancer and DDS . Jpn. J. Cancer Chemother. , 21 , 736 – 737 ( 1994. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 4. ) Kotz , K. W. and Schilder , R. J.High‐dose chemotherapy and hematopoietic progenitor cell support for patients with epithelial ovarian cancer . Semin. Oncol. , 22 , 250 – 262 ( 1995. ). [PubMed] [Google Scholar]
  • 5. ) Malmstorm , H. , Carstensen , J. and Simonsen , E.Experience with implanted subcutaneous ports for intraperitoneal chemotherapy in ovarian cancer . Gynecol. Oncol. , 54 , 27 – 34 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Markman , M.Intraperitoneal cisplatin and carboplatin in the management of ovarian cancer . Semin. Oncol. , 21 , 17 – 19 ( 1994. ). [PubMed] [Google Scholar]
  • 7. ) Noda , T. , Saitoh , S. , Ando , Y. , Nakanishi , A. , Maruya , C. , Yoh , S. , Hino , K. , Kiyozuka , Y. and Ichijou , M.Intraperitoneal (IP) high‐dose cisplatinum (CDDP) chemotherapy in patients with advanced ovarian cancer . J. Jpn. Soc. Cancer Ther. , 20 , 797 – 807 ( 1985. ). [PubMed] [Google Scholar]
  • 8. ) Ryuko , K. , Iwanari , O. , Moriyama , M. , Moriyama , S. , Nakayama , O. , Miyako , J. and Kitao , M.Intraperitoneal chemotherapy through implantable injection port in patients with advanced ovarian (or tubal) carcinoma . Jpn. J. Cancer Chemother. , 18 , 2052 – 2057 ( 1991. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 9. ) Noda , T. , Oku , M. , Kiyozuka , Y. , Ninomiya , Y. , Hino , K. , Okamura , Y. , Maruyama , M. and Ichijou , M.Intraperitoneal high‐dose cisplatinum chemotherapy (CDDP‐ip) in patients with carcinomatous peritonitis . Jpn. J. Cancer Chemother. , 14 , 1025 – 1032 ( 1987. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 10. ) Jones , R. B. , Collins , J. M. , Myers , C. E. , Brooks , A. E. , Hubbard , S. M. , Balow , J. E. , Brennan , M. F. , Dedrick , R. L. and DeVita , V. T.High‐volume intraperitoneal chemotherapy with methotrexate in patients with cancer . Cancer Res. , 41 , 55 – 59 ( 1981. ). [PubMed] [Google Scholar]
  • 11. ) Dedrick , R. L. , Myers , C. E. , Bungy , P. M. and DeVita , V. T. , Jr.Pharmakokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer . Cancer Treat. Rep. , 62 , 1 – 11 ( 1978. ). [PubMed] [Google Scholar]
  • 12. ) Myers , C. E. and Collins , J. M.Pharmacology of intraperitoneal chemotherapy . Cancer Invest. , 1 , 395 – 407 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Hirabayashi , K.Intraperitoneal chemotherapy . Jpn. J. Cancer Chemother. , 16 , 180 – 186 ( 1989. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 14. ) Pretorius , G. R. , Petrilli , S. E. , Kean , C. , Ford , C. L. , Hoeschele , D. J. and Lagasse , D. L.Comparison of the iv and ip routes of administration of cisplatin in dogs . Cancer Treat. Rep. , 65 , 1055 – 1062 ( 1981. ). [PubMed] [Google Scholar]
  • 15. ) Rusznyak , I. , Foldi , M. and Szabo , G.In “ Lymphatics and Lymph Circulation ,” pp. 475 – 510 ( 1967. ). Pergamon Press; , London . [Google Scholar]
  • 16. ) Ikada , Y. , Kyo , M. and Hyon , S.‐H.Preparation of biodegradable microspheres for sustained release of cisplatin . Proc. Int. Symp. Control Relat. Bioact. Mater. , 20 , 462 – 463 ( 1993. ). [Google Scholar]
  • 17. ) Ike , O. , Shimizu , Y. , Wada , R. , Hyon , S.‐H. and Ikada , Y.Controlled cisplatin delivery system using poly(D, L‐lactic acid) . Biomaterials , 13 , 230 – 234 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Sugiyama , T. , Yokota , D. , Ushijima , K. , Imaishi , K. , Hirakawa , N. , Nakanami , M. , Nishida , T. and Yakushiji , M.An experimental model for advanced ovarian cancer . Kurume Med. , 37 , 15 – 21 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Imaishi , K.Intraperitoneal transplantation of ascitic cancer cells from a 7,12‐dimethylbenz(α)anthracene (DMBA)‐induced ovarian cancer . Kurume Med. , 39 , 195 – 201 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Ike , O. , Wada , R. , Kusanoi , Y. , Watanabe , S. , Hyon , S.‐H. , Ikada , Y. and Shimizu , Y.Cis‐diamminedichlo‐roplatinum delivery system using poly (lactic acid) . Drug Delivery Syst. , 5 , 29 – 32 ( 1990. ). [Google Scholar]
  • 21. ) Hagiwara , A. , Takahashi , T. , Kojima , O. , Tamaguchi , T. , Sasabe , T. , Lee , M. , Sakakura , C. , Shoubayashi , S. , Ikada , Y. and Hyon , S.‐H.Pharmacologic effects of cisplatin microspheres on peritoneal carcinomatosis in rodents . Cancer , 71 , 844 – 850 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Hagiwara , A. , Takahashi , T. , Sasabe , T. , Ito , M. , Lee , M. , Sakakura , C. , Shoubayashi , S. , Muranishi , S. and Tashima , S.Toxicity of a new dosage format, cisplatin incorporated in lactic acid oligomer microspheres, in mice . Anti-Cancer Drugs , 3 , 237 – 244 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Hagiwara , A. , Takahashi , T. , Sasabe , T. , Itou , M. , Yoneyama , C. , Shimotsuma , M. , Iwamoto , A. , Wada , R. , Hyon , S.‐H. , Ikada , Y. , Kusanoi , Y. and Muranishi , S.Superior therapeutic effects of cisplatin incorporated in lactic acid oligomer microspheres on peritoneal carcinomatosis in mice . J. Clin. Exp. Med. , 152 , 613 – 614 ( 1990. ) ( in Japanese ). [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES