5-氟尿嘧啶聚乳酸微球防治增殖性玻璃体视网膜病变的安全性研究

目的探讨自制5-氟尿嘧啶聚乳酸微球的药物特性及安全性。方法通过恒温振荡法观察5-氟尿嘧啶聚乳酸微球体外释药特性;采用60Co灭菌方法消毒灭菌;5-氟尿嘧啶聚乳酸微球植入小鼠背部皮下,隔日处死小鼠后观察皮肤及微球,以检测微球的体内稳定性;将微球植入玻璃体腔后,定期测定房水中药物含量,观察其体内释药特性,并分别于注药前及注药后第2d、5d、9d、14d行F-ERG检查,于第28d时将动物处死,行组织病理学检查,以及扫描电镜、透射电镜检查,观察5-FU微球对角膜、房角、视网膜的影响。结果5-氟尿嘧啶聚乳酸微球在体外释药672h,累积释放百分率为72.3%,具有明显的缓释作用;60Co灭菌后药物含量及形态无明显变化;小鼠皮下埋植1月后,微球有破碎粘连现象,微球在小鼠体内组织相容性良好;房水中药物含量测定表明氟尿嘧啶聚乳酸微球有明显的缓释作用,体内药物浓度在较长时间维持较高水平,T1/2为379.05h;视网膜电流图潜时及波幅注药前后无明显改变,组织学检查及电镜检查,注药眼与对照眼未见明显差别。结论本研究制备的氟尿嘧啶聚乳酸微球具有明显的缓释作用,60Co灭菌方法可靠,体内药物浓度在较长时间维持较高水平,注入玻璃体腔后未产生明显的毒副作用。5-氟尿嘧啶聚乳酸微球有望成为一种理想的抑制增殖性玻璃体视网膜病变的方法。

Safety of 5-fluorouracil polyactic acid microsphere in prevention of proliferative vitreoretinopathy

Objective To study the features and safety of 5 - fluorouracil polyactic acid microsphere. Methods To observe 5 - fluorouracil polyactic acid microsphere release features in vitro by shaking in stable temperature. After ^60Co radiation, microsphere was implanted inside the dorsal skin of mice. The skin and the microsphere were observed after mice were sacrificed every other days. To implant microsphere into vitreous cavity. Drug content in aqueous humor was measured regularly. Flash ERG was repeated on the 2^nd, 5^th, 9^th and 14^th day after implantation. Rats were sacrificed on the 28^th day after implantation. Scanning and transmitted electrical microscope were used to evaluate the effect on cornea, chamber angle and retina of microsphere. Results The cumulated drug release ratio is 72. 3% as 5 - fluorouracil polyactic acid microsphere released in vitro for 672hrs. It shows controlled release ability. Drug content and form characteristics showed no change after ^60Co radiation. After 1 month since implantation inside mice skin, microsphere showed breaks and adherence with good histocompatibility. Drug content of aqueous humor measurement confirmed the controlled release characteristics. Drug concentration in vivo maintains high level. Its half life T1/2 is 379. 05h. Latent and amplitude of ERG showed no change after implantation of microsphere into vitreous cavity. Histology and electrical microscope examination showed no change, too. Conclusions 5 - fluorouracil polyactic acid microsphere of this study possesses good controlled release characteristics. 6o Co radiation is an effective sterilization way. Drug content in vivo can keep high level for a long time. No prominent side effect or complication occurred after implantation into the vitreous cavity. 5 - fluorouracil polyactic acid microsphere will become an excellent way for prevention of proliferative vitreoretinopathy.