眼用海藻酸钠-维甲酸微球药物代谢动力学的实验研究

目的探讨由维甲酸和海藻酸钠制成海藻酸钠-维甲酸(AGS-RA)微球药物缓释系统的动物体内外药物释放特点。方法有机溶剂将维甲酸溶解,与1.5%的海藻酸钠均匀混合,用静电微囊发生器一次成型制作海藻酸盐-维甲酸微球;镜下观察测量微球的形态和大小,并用紫外分光光度仪测定微球的药物含量;体外释药实验则通过紫外分光光度仪和高压液相的方法测定 RA 的体外释放规律;体内实验则是通过玻璃体腔注入 AGS-RA 药物微球,利用高压液相的方法观察微球的房水药代动力学特点。结果 AGS-RA 微球经测定,大小是(95.2443±8.6265)μm;药物包含量是(1.7644±0.0453)μg/mg;体外实验表明 AGS-RA 微球的 RA 药物在观察的28d 内均匀释放;房水药代动力学研究显示药物在6周内基本均匀释放[1、3d,1、2、3、4、5、6周房水 RA 浓度分别是(23.79±0.15)、(33.45±0.48)、(19.95±0.79)、(21.12±0.47)、(19.65±0.35)、(20.01±0.25)、(18.24±0.27)、(18.5±0.68)ng/ml],仅第3天有1个释放峰。结论兔体内外实验表明,AGS-RA 微球可对药物RA 起缓释作用。

The dynamic study of retinoic acid and its alginate sodium microspheres in rabbit eye

OBJECTIVE: To obtain a intravitreous delay release system by injection of biodegradable polymers (alginate sodium-retinoic acid microspheres, AGS-RA microspheres) to the rabbit vitreous and study the release character of RA delivery system in vitro. METHODS: RA was mixed with 1.5% alginate sodium and microspheres was made by a special electrostatic generator after dissolved in organic solvent; The content of AGS-RA in the microspheres and its release from the microspheres were measured by spectrophotometer. The characteristic of the metabolic dynamics of AGS-RA in the microspheres was analyzed by HPLC. RESULTS: The size of microspheres we manufacture is (95.2443 +/- 8.6265) microm; Medicine contain quantity of RA is (1.7644 +/- 0.0453) microg/mg; Vitro test show that RA in the microspheres is release evenly in the 28 days of observation; Inject medicine to vitreous cavity show no poisonous side effect; The medicine dynamics research of microspheres showed that medicine is being even in 6 weeks releasing [the aqueous RA density of 1, 3 d, 1, 2, 3, 4, 5, 6 weeks is (23.79 +/- 0.15), (33.45 +/- 0.48), (19.95 +/- 0.79), (21.12 +/- 0.47), (19.65 +/- 0.35), (20.01 +/- 0.25), (18.24 +/- 0.27), (18.5 +/- 0.68) ng/ml, respectively]. Just in the 3rd day there is a release summit. CONCLUSION: In vivo and in vitro tests show that AGS-RA microspheres can delay RA release uniformity.