Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model

被引：126

作者：

Bernardi, Andressa ^{[1
]}

Braganhol, Elizandra ^{[1
]}

Jaeger, Eliezer ^{[2
]}

Figueiro, Fabricio ^{[1
]}

Edelweiss, Maria Isabel ^{[3
]}

Pohlmann, Adriana R. ^{[2
,4
]}

Guterres, Silvia S. ^{[2
]}

Battastini, Ana M. O. ^{[1
]}

机构：

[1] Univ Fed Rio Grande do Sul, Dept Bioquim, Inst Ciencias Basicas Saude, BR-90035003 Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Programa Posgrad Ciencias Farmaceut, Fac Farm, BR-90035003 Porto Alegre, RS, Brazil

[3] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Dept Patol, BR-90035003 Porto Alegre, RS, Brazil

[4] Univ Fed Rio Grande do Sul, Programa Posgrad Quim, Inst Quim, BR-90035003 Porto Alegre, RS, Brazil

来源：

CANCER LETTERS | 2009年 / 281卷 / 01期

关键词：

Glioblastoma multiform; Cell proliferation; Indomethacin; Polymeric nanocapsules; Drug delivery; SOLID LIPID NANOPARTICLES; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BRAIN-TUMORS; CYANOACRYLATE) NANOPARTICLES; CELL LINES; NESTIN EXPRESSION; DELIVERY; POLY(EPSILON-CAPROLACTONE); CHEMOTHERAPY; NANOSPHERES;

D O I：

10.1016/j.canlet.2009.02.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Multimodal combinations of target agents with radiation and chemotherapy may enhance cancer treatment efficacy; however, despite these treatments, gliomas recur early due to their highly proliferative, infiltrative and invasive behaviors. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted intensive interest in recent years since they may provide a sustained, controlled and targeted delivery. In the present study, we investigated the effect of indomethacin-loaded nanocapsules in an experimental glioma model. The rats treated with indomethacin-loaded nanocapsules demonstrated a significant reduction in tumor size and half of these animals presented just cells with characteristics of a residual tumor. as shown by immunostaining for nestin. Pathological analyses showed that the treated gliomas presented a significant reduction in the mitotic index and other histological characteristics that indicate a less invasive/proliferative tumor. An important finding of the present study is that indomethacin carried by polymeric nanocapsules achieved higher intracerebral drug concentrations than those of indomethacin in solution. Furthermore, indomethacin achieved a greater concentration in the hemisphere where the glioma was implanted, compared with the contralateral healthy hemisphere. Indomethacin-loaded nanocapsule treatment did not Cause characteristics of toxicity and increased the survival of animals. Thus, our results show that polymeric nanocapsules are able to increase the intratumoral bioavailability of indomethacin and reduce the growth of implanted gliomas. Data suggest that indomethacin-loaded nanocapsules could offer new and potentially highly effective strategies for the treatment of malignant gliomas. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：53 / 63

页数：11

共 51 条

[1] Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastoma-bearing rats [J].