神经生长因子巩膜外缓释给药的研究

Experimental study on directional control-released delivery of NGF through sclera

目的探讨巩膜外植入神经生长因子（NGF）药膜后其眼内的药代动力学改变，研究该药膜是否有缓释效果，改善NGF给药途径。方法筛选与NGF有亲和力的胶原组织，制成具有单向缓释功能的药膜，将其植入健康白兔巩膜表面，朋ELISA法测定并观察对照组和实验组各时间点玻璃体内NGF质量浓度的变化，用3P97药代动力学程序计算主要药代动力学参数。结果实验组在药膜植入后2～15d内NGF质量浓度明显高于对照组，第18d降至正常。第3d达到峰质量浓度20．911g／ml，半衰期约7．41d。药一时曲线下面积AUC0-18为232．78801ng·d／ml。结论自制NGF药膜可缓释进入玻璃体，其峰浓度较高，消除半衰期较长，质量浓度波动较小.

Objective Nerve growth factor （NGF） is protein neurotrophic factor and it is difficult to topically use in ophthahnology. Our experiment observed the intravitreal pharmacokineties of control-released NGF drug membrane implanted into the subconjunctiva and outside the sclera of the rabbits and investigated the slow release ability of NGF drug membrane. Methods Sixty rabbits were divided into ten groups,and 6 rabbits were selected randomly as the control group. Unidirectional NGF-collagen control-released membranes were prepared and embedded beneath the inferior rectus muscle in the right eyes of rabbits from 9 experimental groups. Rabbit vitreous specimen were obtained in 2,3,6,8,9, 11, 12, 15 and 18 days after experiment. NGF concentratinn alteration in vitreous were measured by BAS-ELISA method and the pharmacnkinetie change was computed by 3P97 software. Results NGF level in vitreous body was decreased slowly with time lapse in experimental groups, and the NGF concentrations in vitreous within 2 - 15 days were higher than that of control group. The NGF level decreased to normal on the 18th day. The maximum concentration of NGF in experimental groups was 20.91 ng/rid on the 3rd day. The half-life for elimination（t1/2） of NGF from vitreous was about 7.41 days. The area under concentration-time eurve（AUC0-t） was 232. 788 01 ng · d/ml. Conclusion The NGF-collagen control-released membranes are able to release NGF regularly and penetrate the wall of eyeball into the intraocular tissue and accumulate in vitreous body. It has a higher Cmax and longer half-life. The NGF concentration in vitreous decline with less fluctuation.