Kim So Yeon, Lee Young Moo, Baik Doo J, Kang Ju S
Department of Biomedical Engineering, School of Chemical Engineering, College of Engineering, Hanyang University, Seoul 133-791, South Korea.
Biomaterials. 2003 Jan;24(1):55-63. doi: 10.1016/s0142-9612(02)00248-x.
Amphiphilic diblock polymeric nanospheres composed of methoxy poly(ethylene glycol) (MePEG) and poly(epsilon-caprolactone)(PCL) was prepared for application as a novel drug carrier. We could obtain the MePEG/PCL nanospheres that exhibited an average diameter of less than 200 nm with narrow size distribution and a relatively high drug-loading efficiency of about 41.98% and 20.8% for indomethacin and paclitaxel, respectively. To estimate the toxicity of nanospheres, we investigated cytotoxicity using the normal human fibroblast, the median lethal dose (LD(50)) and various organ toxicities using male ICR mice. The indomethacin-loaded nanosphere showed higher cell viability than indomethacin in the cytotoxicity test using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The LD(50) of MePEG/PCL nanospheres determined by Litchfield-Wilcoxon method was 1.47 g/kg. After the mice were intraperitoneally injected with MePEG/PCL nanospheres as a half-dose level of LD(50) for 7 days, no significant histopathologic changes were observed in MePEG/PCL nanospheres-treated mice compared with normal mice in the light and electron microscopic observations of various organs such as heart, lung, liver and kidney. It was suggested that MePEG/PCL nanospheres might be useful candidate as a novel injectable drug carrier for hydrophobic drugs such as indomethacin and paclitaxel.
由甲氧基聚（乙二醇）（MePEG）和聚（ε-己内酯）（PCL）组成的两亲性二嵌段聚合物纳米球被制备用作新型药物载体。我们能够获得平均直径小于200nm、尺寸分布窄的MePEG/PCL纳米球，吲哚美辛和紫杉醇的载药效率相对较高，分别约为41.98%和20.8%。为了评估纳米球的毒性，我们使用正常人成纤维细胞研究了细胞毒性，使用雄性ICR小鼠研究了半数致死剂量（LD(50)）和各种器官毒性。在使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）法的细胞毒性试验中，载吲哚美辛的纳米球显示出比吲哚美辛更高的细胞活力。通过Litchfield-Wilcoxon方法测定的MePEG/PCL纳米球的LD(50)为1.47g/kg。在以LD(50)的半剂量水平给小鼠腹腔注射MePEG/PCL纳米球7天后，在心脏、肺、肝和肾等各种器官的光镜和电镜观察中，与正常小鼠相比，MePEG/PCL纳米球处理的小鼠未观察到明显的组织病理学变化。提示MePEG/PCL纳米球可能是吲哚美辛和紫杉醇等疏水性药物新型注射用药物载体的有用候选物。
