2013年11月
A novel drug delivery system of intraperitoneal chemotherapy for peritoneal carcinomatosis using gelatin microspheres incorporating cisplatin
SURGERY
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- ,
- ,
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- 巻
- 154
- 号
- 5
- 開始ページ
- 991
- 終了ページ
- 999
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.surg.2013.04.054
- 出版者・発行元
- MOSBY-ELSEVIER
Background. Peritoneal carcinomatosis is a poor prognostic factor for patients with gastrointestinal, gynecologic, and pancreatic cancer. Cisplatin (CDDP) is among the most effective anti-cancer agents, although its adverse effects remain unresolved. For the treatment of peritoneal carcinomatosis with high-dose CDDP, it is necessary to design a new delivery system of CDDP that can decrease systemic toxicity and achieve a better targeted, high-dose chemotherapy.
Methods. Microspheres were prepared from gelatin of a nontoxic, biodegradable material for the sustained release of CDDP. The gelatin microspheres incorporating CDDP (GM-CDDP) were injected intraperitoneally into a mouse model of peritoneal carcinomatosis; their therapeutic efficacy and adverse effects were evaluated in comparison with intraperitoneal administration of free CDDP.
Results. GM-CDDP released CDDP in the peritoneal cavity as a result of gelatin biodegradation. Mice treated with microspheres in the peritoneal cavity lived longer than mice treated with free CDDP (74 +/- 23 vs 40 +/- 23 days; P < .05). The mice treated with GM-CDDP also lost no Weight, whereas the free CDDP group lost approximately 20% body weight (106 +/- 5% vs 80 +/- 7%; P < .001; body weight on day 1 = 100%). GM-CDDP significantly decreased the nephrotoxicity and hematotoxicity of CDDP.
Conclusion. GM decreased the adverse effects of CDDP and allowed high-dose intraperitoneal chemotherapy with the control of CDDP. This technique of gradual local release may allow us to provide a high-dose, targeted, intraperitoneal chemotherapy with CDDP, resulting in enhanced anti-cancer effects. These gelatin microspheres may be useful as a drug carrier for the treatment of peritoneal carcinomatosis.
Methods. Microspheres were prepared from gelatin of a nontoxic, biodegradable material for the sustained release of CDDP. The gelatin microspheres incorporating CDDP (GM-CDDP) were injected intraperitoneally into a mouse model of peritoneal carcinomatosis; their therapeutic efficacy and adverse effects were evaluated in comparison with intraperitoneal administration of free CDDP.
Results. GM-CDDP released CDDP in the peritoneal cavity as a result of gelatin biodegradation. Mice treated with microspheres in the peritoneal cavity lived longer than mice treated with free CDDP (74 +/- 23 vs 40 +/- 23 days; P < .05). The mice treated with GM-CDDP also lost no Weight, whereas the free CDDP group lost approximately 20% body weight (106 +/- 5% vs 80 +/- 7%; P < .001; body weight on day 1 = 100%). GM-CDDP significantly decreased the nephrotoxicity and hematotoxicity of CDDP.
Conclusion. GM decreased the adverse effects of CDDP and allowed high-dose intraperitoneal chemotherapy with the control of CDDP. This technique of gradual local release may allow us to provide a high-dose, targeted, intraperitoneal chemotherapy with CDDP, resulting in enhanced anti-cancer effects. These gelatin microspheres may be useful as a drug carrier for the treatment of peritoneal carcinomatosis.
- リンク情報
- ID情報
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- DOI : 10.1016/j.surg.2013.04.054
- ISSN : 0039-6060
- Web of Science ID : WOS:000326432100006