CAJ | 학술논문

目的探讨低分子肝素缓释系统防治兔后发性白内障的有效性和安全性.方法采用前瞻性随机分组对照研究.以乳酸-羟基乙酸共聚物(PLGA)为载体采用冻干法制备低分子肝素缓释系统(LMWH DDS)并体外评价其缓释特性.将50只(50只眼)新西兰白兔分别行超声乳化透明晶状体吸除术,并随机均分为5组:A组术后生理盐水滴眼,B、C、D组术毕后房分别植入载药量为1.00 mg、0.50 mg、0.25 mg的LMWH DDS,E组植入不含药物的空白缓释系统;术后12周对术眼行裂隙灯显微镜、组织病理学以及电镜检查,并检测房水药物浓度和晶状体后囊膜湿重.术后房水闪光、房水细胞分级以及后囊膜混浊分级资料采用Kruskal-Wallis检验,房水药物浓度采用具有一个重复测量因素的两因素方差分析.结果采用冻干法制备的LMWH DDS包封率为98.2%,体外释药方程拟合以零级方程为佳.术后B、C、D组炎症反应较A、E组显著减轻;术后12周A、B、C、D、E各组后囊膜混浊发生率分别为100%(10/10)、20%(2/10)、30%(3/10)、90%(9/10)、100%(10/10),后囊膜混浊分级评分组间比较差异均具有统计学意义(X~2=31.637,P=0.000),后囊膜湿重分别为(114.59±14.58)mg、(24.14±6.08)mg、(39.23±17.13)mg、(99.35±29.37)rag、(115.29±19.87)mg,组间比较差异均具有统计学意义(F=42.149,P=0.000);术后4周内B、C组房水中低分子肝素一直维持较高浓度(大于20 ms/L),D组浓度较低且不稳定;光镜和电镜下B、C组后囊细胞增生不活跃,未发现眼内毒性反应;术后均未见眼内出血现象.结论以PLGA为载体采用冻干法制备的LMWHDDS具有良好的缓释性和组织相容性;其后房植入能明显减轻术后炎症反应,能安全、有效抑制后发性白内障的发生,且存在一定量效关系.
목적 탐토저분자간소완석계통방치토후발성백내장적유효성화안전성.방법 채용전첨성수궤분조대조연구.이유산-간기을산공취물(PLGA)위재체채용동간법제비저분자간소완석계통(LMWH DDS)병체외평개기완석특성.장50지(50지안)신서란백토분별행초성유화투명정상체흡제술,병수궤균분위5조:A조술후생리염수적안,B、C、D조술필후방분별식입재약량위1.00 mg、0.50 mg、0.25 mg적LMWH DDS,E조식입불함약물적공백완석계통;술후12주대술안행렬극등현미경、조직병이학이급전경검사,병검측방수약물농도화정상체후낭막습중.술후방수섬광、방수세포분급이급후낭막혼탁분급자료채용Kruskal-Wallis검험,방수약물농도채용구유일개중복측량인소적량인소방차분석.결과 채용동간법제비적LMWH DDS포봉솔위98.2%,체외석약방정의합이령급방정위가.술후B、C、D조염증반응교A、E조현저감경;술후12주A、B、C、D、E각조후낭막혼탁발생솔분별위100%(10/10)、20%(2/10)、30%(3/10)、90%(9/10)、100%(10/10),후낭막혼탁분급평분조간비교차이균구유통계학의의(X~2=31.637,P=0.000),후낭막습중분별위(114.59±14.58)mg、(24.14±6.08)mg、(39.23±17.13)mg、(99.35±29.37)rag、(115.29±19.87)mg,조간비교차이균구유통계학의의(F=42.149,P=0.000);술후4주내B、C조방수중저분자간소일직유지교고농도(대우20 ms/L),D조농도교저차불은정;광경화전경하B、C조후낭세포증생불활약,미발현안내독성반응;술후균미견안내출혈현상.결론 이PLGA위재체채용동간법제비적LMWHDDS구유량호적완석성화조직상용성;기후방식입능명현감경술후염증반응,능안전、유효억제후발성백내장적발생,차존재일정량효관계.
Objective To investigate the safety and efficacy of low-molecular-weight heparin drug delivery system(LMWH DDS) for prevention of posterior capsular opacification (PCO) in rabbit eyes.Methods (1) To prepare the LMWH DDS by freeze-drying way with Polylactic-co-glycolic acid (PLGA) as the cartier, and evaluate its release properties in vitro.(2) Fifty New Zealand albino rabbits (50 eyes)undergoing phacoemulsification were equally divided into five groups: receiving normal saline eye drops (group A), 3 different dose (1 mg, 0.5 mg and 0.25 mg) of LMWH DDS respectively implanted into the posterior chamber (group B, C and D), and a carrier DDS implanted into the posterior chamber (group E).All the 50 eyes were examined by slit-lamp microscopy.The low-molecular-weight heparin levels in aqueous humor were measured, and the wet posterior capsules were weighed.Results The LMWH DDS prepared with a freeze-dried way has high encapsulation efficiency, and the equation of 49-day release curve fitting in vitro were were similar to zero order.The fibrin exudation in group B, C and D were lower than in Group A and E during the first postoperative day.There were 10, 2, 3, 9 and 10 eyes that developing PCO in the group A, B, C, D and E, respectively.The mean wet-weight of the posterior capsule were ( 114.59± 14.58) mg,(24.14±6.08) mg, (39.23±17.13) mg,(99.35±29.37) mg,(115.29v19.87) mg respectively in 5 trial groups.There were stable and high concentration of low molecular weight heparin in aqueous of group B and C during the 4 weeks ( > 20 mg/L), while a instable and lower concentrations in group D.The result of optical microscopy and electron microscopy examination indicated that fibroblast proliferation was quite active in groups A, D and E, but inactive in group B and C.Neither infiltration of inflammatory cells at the cornea, iris, trabecular meshwork and ciliary body nor retinal degeneration or necrosis was found in any group at 12 weeks.There was no introcular bleeding in all the five groups in the following 12 weeks.Conclusions The LMWH DDS prepared by freeze-drying way with PLGA as the carrier has good slow-release and biological tolerance, Implantion of LMWH DDS into the posterior chamber of experimental animals can significantly reduce postoperative fibrin exudation, and can safe and effective prevent the occurrence of PCO, and also there were some dose-effect relationship.