Xie Jingwei, Wang Chi-Hwa
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117576, Singapore.
Pharm Res. 2006 Aug;23(8):1817-26. doi: 10.1007/s11095-006-9036-z.
The present study aims to develop electrospun PLGA-based micro- and nanofibers as implants for the sustained delivery of anticancer drug to treat C6 glioma in vitro.
PLGA and an anticancer drug--paclitaxel-loaded PLGA micro- and nanofibers were fabricated by electrospinning and the key processing parameters were investigated. The physical and chemical properties of the micro- and nanofibers were characterized by various state-of-the-art techniques, such as scanning electron microscope and field emission scanning electron microscope for morphology, X-ray photoelectron spectroscopy for surface chemistry, gel permeation chromatogram for molecular weight measurements and differential scanning calorimeter for drug physical status. The encapsulation efficiency and in vitro release profile were measured by high performance liquid chromatography. In addition, the cytotoxicity of paclitaxel-loaded PLGA nanofibers was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide MTT) assay on C6 glioma cell lines.
PLGA fibers with diameters of around several tens nanometers to 10 microm were successfully obtained by electrospinning. Ultrafine fibers of around 30 nm were achieved after addition of organic salts to dilute polymer solution. The encapsulation efficiency for paclitaxel-loaded PLGA micro- and nanofibers was more than 90%. DSC results suggest that the drug was in the solid solution state in the polymeric micro- and nanofibers. In vitro release profiles suggest that paclitaxel sustained release was achieved for more than 60 days. Cytotoxicity test results suggest that IC50 value of paclitaxel-loaded PLGA nanofibers (36 microg/ml, calculated based on the amount of paclitaxel) is comparable to the commercial paclitaxel formulation-Taxol.
Electrospun paclitaxel-loaded biodegradable micro- and nanofibers may be promising for the treatment of brain tumour as alternative drug delivery devices.
本研究旨在开发基于电纺聚乳酸-羟基乙酸共聚物(PLGA)的微米和纳米纤维作为植入物,用于在体外持续递送抗癌药物以治疗C6胶质瘤。
通过静电纺丝制备PLGA以及负载抗癌药物紫杉醇的PLGA微米和纳米纤维,并研究关键加工参数。微米和纳米纤维的物理和化学性质通过各种先进技术进行表征,如用于形态学的扫描电子显微镜和场发射扫描电子显微镜、用于表面化学的X射线光电子能谱、用于分子量测量的凝胶渗透色谱以及用于药物物理状态的差示扫描量热仪。通过高效液相色谱法测量包封率和体外释放曲线。此外,使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法在C6胶质瘤细胞系上评估负载紫杉醇的PLGA纳米纤维的细胞毒性。
通过静电纺丝成功获得了直径约几十纳米至10微米的PLGA纤维。添加有机盐以稀释聚合物溶液后,获得了约30纳米的超细纤维。负载紫杉醇的PLGA微米和纳米纤维的包封率超过90%。差示扫描量热法结果表明,药物在聚合物微米和纳米纤维中呈固溶体状态。体外释放曲线表明,紫杉醇实现了超过60天的持续释放。细胞毒性测试结果表明,负载紫杉醇的PLGA纳米纤维的半数抑制浓度(IC50)值(基于紫杉醇的量计算为36微克/毫升)与商业紫杉醇制剂泰素相当。
电纺负载紫杉醇的可生物降解微米和纳米纤维作为替代药物递送装置,在治疗脑肿瘤方面可能具有前景。