Treatment of Rat Brain Tumors Using Sustained-Release of Camptothecin from Poly(lactic-co-glycolic acid) Microspheres in a Thermoreversible Hydrogel

被引：25
作者：
Ozeki, Tetsuya [1 ]
Hashizawa, Kosuke [2 ]
Kaneko, Daiki [2 ]
Imai, Yoshihiro [2 ]
Okada, Hiroaki [2 ]
机构：
[1] Nagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, Aichi 4678603, Japan
[2] Tokyo Univ Pharm & Life Sci, Sch Pharm, Tokyo 1920392, Japan
来源：
CHEMICAL & PHARMACEUTICAL BULLETIN | 2010年 / 58卷 / 09期
关键词：
brain tumor; thermoreversible gelation polymer; sustained release; poly(lactic-co-glycolic acid) microsphere; camptothecin; DNA TOPOISOMERASE-I; SYNTHETIC HYDROGEL; INJECTABLE MICROSPHERES; LEUPRORELIN ACETATE; AGENT-CAMPTOTHECIN; MALIGNANT GLIOMAS; DELIVERY; GELATION; CHEMOTHERAPY; NSC-100880;
D O I：
10.1248/cpb.58.1142
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A thermoreversible gelation polymer consisting of an aqueous solution in the sol state at room temperature and in the gel state near body temperature was examined for its use in the retention of microspheres and sustained, long-term delivery of anti-cancer drugs using a rat model of malignant glioma. The poly(lactic-co-glycolic acid) (PLGA) microspheres containing camptothecin at ratios of 1 : 33 or 1 : 50 mediated sustained release, with approximate 80% of camptothecin released after 28 d. Rats were inoculated in the brain with C6 glioma cells, followed 7 d later by injection in the tumor site with 1 : 33 and 1 : 50 PLGA microspheres dispersed in a thermoreversible gelation polymer (TGP) solution. Kaplan-Meier analysis showed that the mean survival period of the untreated group was 16 d, with a slight increase in rats treated with TGP-only solution, empty or 1 : 50 microspheres in phosphate-buffered saline. The mean survival period of rats treated with the camptothecin powder in TGP was 21 d, while that of rats treated with 1 : 33 and 1 : 50 microspheres in TGP was significantly longer than the untreated group; long-term survival rats were observed. These results suggest that the anti-tumor effect of camptothecin can be enhanced by long-term sustained release from microspheres retained in the rat brain by TGP gel.
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收藏
页码：1142 / 1147
页数：6
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