Preparation of camptothecin-loaded PCEC microspheres for the treatment of colorectal peritoneal carcinomatosis and tumor growth in mice
Preparation of camptothecin-loaded PCEC microspheres for the treatment of colorectal peritoneal carcinomatosis and tumor growth in mice
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DOI：
10.1016/j.canlet.2011.08.007
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发表时间：
2011-12-22
期刊：
影响因子：
9.7
通讯作者：
Qian, ZhiYong
中科院分区：
文献类型：
--
作者：
Dai, Mei;Xu, Xu;Qian, ZhiYong
本研究的目的是制备PCL-PEG-PCL （PCEC）微球，以保护喜树碱不被水解，延长其释放时间，提高其对小鼠结直肠癌腹膜癌病变和肿瘤生长的治疗效果。采用油包水乳状溶剂蒸发法制备了喜树碱（CPT）负载PCL-PEG-PCL （PCEC）微球。研究了负载cpt的PCEC微球的粒径、形态特征、包封效率、体外释药研究和体外细胞毒性。对Balb/c雄性结直肠癌小鼠进行了体内研究。加载cpt的PCEC微球每周1次应用于小鼠腹腔。游离CPT作为阳性对照。治疗第14天，处死小鼠，评价cpt负载PCEC微球的抗肿瘤活性。与对照组相比，cpt负载PCEC微球治疗组肿瘤淋巴结数量明显减少。CD34免疫组化染色肿瘤组织显示，cpt - PCEC微球处理组MVD阳性细胞明显减少（P < 0.05）。cpt负载的PCEC微球被认为对治疗结肠癌腹部转移有潜在的作用。2011爱思唯尔爱尔兰有限公司版权所有。
The aim of this study was to prepare PCL-PEG-PCL (PCEC) microspheres to protect camptothecin from hydrolysis, to extend its release time and to enhance its treatment efficacy on colorectal peritoneal carcinomatosis and tumor growth in mice. Camptothecin (CPT)-loaded PCL-PEG-PCL (PCEC) microspheres were prepared by oil-in-water emulsion solvent evaporation method. The particle size, morphological characteristics, encapsulation efficiency, in vitro drug release studies and in vitro cytotoxicity of CPT-loaded PCEC microspheres have been investigated. In vivo studies were carried out on Balb/c male mice bearing colorectal peritoneal carcinomatosis. CPT-loaded PCEC microspheres were applied to abdominal cavity of mice once a week. Free CPT was used as a positive control. On 14th day of treatment, mice were sacrificed and antitumor activities of CPT-loaded PCEC microspheres were evaluated. Compared with control group, a significant decrease in the number of tumor nodes was observed in group treated with CPT-loaded PCEC microspheres. Immunohistochemistry staining of tumor tissues with CD34 revealed that MVD positive cells were significantly reduced in CPT-loaded PCEC microspheres treated group in contrast to other groups (P < 0.05). The CPT-loaded PCEC microspheres were considered potentially useful to treat the abdominal metastases of colon carcinoma. (C) 2011 Elsevier Ireland Ltd. All rights reserved.