替莫唑胺缓释系统的构建及体外抗胶质瘤细胞的实验研究

目的 制作一种安全有效的替莫唑胺(TM)缓释系统，使药物稳定释放，减少突释现象，减少局部使用时的神经毒性。方法 首先通过电纺丝方法制作TM/聚碳酸亚丙酯(PPC)纺丝膜，探论其制作条件，分析纤维直径、载药量和包封率等参数。然后将部分纺丝膜用海藻酸(ALG)包被，在体外观察两种膜片的药物释放速度及对C6胶质瘤细胞的抑制作用。结果 TM/PPC缓释系统仅在纺丝距离为15～20cm、纺丝电压为10～15kV、聚碳酸亚丙酯质量浓度为8%时可以纺出均匀平滑的纺丝膜。纺丝纤维直径约为3μm，持续释放时间为12d。通过包被ALG，能明显减少突释的发生。两种纺丝膜在体外实验中均显示出较强的持续抑制胶质瘤细胞的能力。结论 通过电纺丝方法制作替莫唑胺缓释系统切实可行。通过包被海藻酸，可以减少突释现象，使药物释放曲线更为平缓。

Controlled release system delivering temozolomide for treatment of experimental glioma in vitro

Objective To build an effective controlled release system for Temozolomide(TM) stable delivering with low initial burst and less neurotoxicity.Methods TM-loaded PPC fiber was manufactured by electrospinning.Influences of fabricating parameters on drug release behavior were investigated.The micro-morphology of TM/PPC-fibers was researched using scanning electron microscopy(SEM).Some fiber sheets were then coated with ALG.In vitro,the release speeds of two forms of samples were studied and their cytotoxicity against C6 glioma cells was assessed.Results Uniform and smooth TM/PPC-fibers could be fabricated only when the weight concentration was 8%,the distance was 15-20 cm and the voltage between the nozzle and the collection instrument was 10-15 kV.The fiber diameter was about 3 μm.The sustained release time was 12 days.The initial bursts of drug-fiber sheets were reduced after being covered with ALG.Cell toxicity test results showed that the above two forms of TM/PPC-fibers can continuously inhibited the C6 glioma cell,and the TM/PPC-fiber sheets were strongly cytotoxic.Conclusions Electrospinning is a feasible method to fabricate TM/PPC-fibers,and ALG covering reduces the initial burst,making the TM release curve more smooth.