Moritera T, Ogura Y, Honda Y, Wada R, Hyon S H, Ikada Y
Department of Ophthalmology, Faculty of Medicine, Kyoto University, Japan.
Invest Ophthalmol Vis Sci. 1991 May;32(6):1785-90.
Microspheres of biodegradable polymers were evaluated as a potential controlled-release drug-delivery system in the vitreous. The microspheres were prepared with polymers of poly(lactic acid) or copolymers of glycolic acid and lactic acid. The release of 5-fluorouracil (5-FU) from the microspheres was studied in vitro. Poly(lactic acid) microspheres released 70-85% of total 5-FU over 7 days. Microspheres of polymers with a smaller molecular weight released the drug more rapidly. Copolymer microspheres released 98% of 5-FU over 2 days. The rate of drug release was controllable by changing the molecular weight of the polymers or using a matrix of copolymer. The intravitreal kinetics of the microspheres were studied in ten rabbits in vivo. A suspension of microspheres was injected into the vitreous cavity of five normal eyes and five vitrectomized eyes. By 48 +/- 5.2 days after injection, the microspheres disappeared from the vitreous cavity in the five normal eyes. Clearance from the vitreous cavity was accelerated in the five rabbits that underwent vitrectomy (14 +/- 2.4 days; P less than 0.001). No difference was found in the b waves of electroretinograms before and after injection of the microspheres. The histologic study showed no abnormal findings as a result of the injection. These results suggested that microspheres of biodegradable polymers may be a potential delivery system for the controlled release of drugs in the vitreous.
可生物降解聚合物微球被评估为一种潜在的玻璃体内控释给药系统。这些微球由聚乳酸聚合物或乙醇酸与乳酸的共聚物制备而成。对微球中5-氟尿嘧啶（5-FU）的体外释放情况进行了研究。聚乳酸微球在7天内释放了总量70-85%的5-FU。分子量较小的聚合物微球释放药物的速度更快。共聚物微球在2天内释放了98%的5-FU。通过改变聚合物的分子量或使用共聚物基质，药物释放速率是可控的。在10只兔子体内研究了微球的玻璃体内动力学。将微球悬浮液注入5只正常眼和5只玻璃体切除眼的玻璃体腔。注射后48±5.2天，5只正常眼中的微球从玻璃体腔消失。在接受玻璃体切除术的5只兔子中，玻璃体腔清除加速（14±2.4天；P<0.001）。注射微球前后视网膜电图的b波未发现差异。组织学研究显示注射后无异常发现。这些结果表明，可生物降解聚合物微球可能是一种在玻璃体内控制药物释放的潜在给药系统。
