玻璃体内注射包载盐酸去甲万古霉素的聚N-异丙基丙烯酰胺-聚氧化乙烯纳米粒治疗兔眼混合细菌性眼内炎的效果  

Effects of intravitreal injection with norvancomycin-loaded poly(N-isopropyl acrylamide)-polyethylene oxide nanoparticle for mixed infection of bacterial endophthalmitis in rabbit

作　　者：陈翔[1] 王雨生[1] 王丽曌 陈晓农[3] 徐修礼[4] 马吉献[1] 

机构地区：[1]第四军医大学西京医院眼科、全军眼科研究所,陕西省西安市710032 [2]陕西省西安市古城眼科医院,710014 [3]北京化工大学,北京市100029 [4]第四军医大学西京医院检验科,陕西省西安市710032

出　　处：《眼科新进展》2009年第4期254-258,共5页Recent Advances in Ophthalmology

基　　金：军队医药卫生科研基金资助(编号:06M261);德国洪堡基金会(Alexander von Humboldt Founda-tion)仪器设备捐赠基金(V-8151/02085,To WANG Yu-Sheng)资助~~

摘　　要：目的探讨玻璃体腔内注射包载盐酸去甲万古霉素(norvancomycin,NV)的聚N-异丙基丙烯酰胺-聚氧化乙烯[poly(N-isopropyl acrylamide)-polyethylene oxide,PNIPAAm-PEO]纳米缓释给药系统(NV-PNIPAAm-PEO)治疗兔混合细菌性眼内炎模型的效果。方法选取健康成年新西兰兔50只,每只随机选取1眼向玻璃体腔内注入100×103CFU.L-1的金黄色葡萄球菌和大肠埃希杆菌混合悬液建立眼内炎模型。建模成功后24h,将实验动物随机分为1个空白对照组(A组)和4个实验组(B组、C组、D组和E组),每组10眼。A组不作任何处理;B组、C组、D组和E组分别向玻璃体腔内注入0.1mL的空白纳米粒(20g.L-1)、无菌生理盐水、盐酸去甲万古霉素原药(4.4g.L-1)和NV-PNIPAAm-PEO(20g.L-1)。于给药后第1、2、3、7、14、21、28、42天分别进行临床炎症评分、眼部A/B超检查及组织病理学检查。结果A组、B组和C组各时间点眼内炎病变程度无明显差异;D组和E组炎性反应较A组、B组和C组轻(P<0.005);E组与D组在术后21d内无差异,21d后E组玻璃体腔混浊程度较D组明显减轻(P<0.005)。眼部A/B超检查,术后7d之后A组、B组和C组可见玻璃体内团块状回声伴点状或短线状回声点;D组在42d后仍可见玻璃体腔轻度混浊;E组注药后7-14d可见玻璃体内点线状回声,回声强度较同时期A组、B组和C组弱,21d后未见明显异常回声。组织病理学检查见A组、B组和C组眼球结构被破坏,D组近后极部视盘前方玻璃体腔内少量淋巴细胞及浆细胞浸润,E组眼球结构正常,未见典型炎性细胞。结论NV-PNIPAAm-PEO纳米粒玻璃体腔注射治疗细菌性眼内炎疗效确切,与单纯盐酸去甲万古霉素眼内注射相比,具有缓释及药效持久等特性。Objective To investigate the therapeutic effects of an intravitreal norvancomycin-loaded poly （ N-isopropyl acrylamide ）-polyethylene oxide （ NV- PNIPAAm-PEO） drug delivery system in a rabbit model with mixed infection of bacterial endophthalmitis. Methods Fifty New Zealand rabbits were selected, and one eye of each rabbit was randomly chosen to receive an intravitreal injection of mixed bacterial suspension,which was 100 × 10^3 CFU · L^-1 staphylococcus aurcus and bacillus cull, to build endophthalmitis model. After 24 hours, all models were randomly divided into 5 groups, 10 eyes in each group. Group A：The normal control group ,treated nothing after bacterial suspension injection; Group B： Intravitreal injection of the 0. l mL empty nano- particle; Group C ： Intravitreal injection of sterilized normal sodium; Group D： Intravitreal injection of 4.4 g· L^-1 norvancomycin ; Group E ： Intravitreal injection of 20 g · L^-1 NVPNIPAAm-PEO. The clinical observation, A/B-scan ultrasonography and histopathological examination were performed at time points of 1 day,2 days,3 days,7 days,14 days, 21 days, 28 days, 42 days after operation. Results The inflammation response was lower in groups D, E than that of groups A, B and C （ P 〈 0. 005 ）, and no significant differences anlong groups A, B and C. After 21 days, the inflammation response of vitreous body in group E was lower than that in group D（P〈0. 005） ,but there was no statistical difference between two groups during 21 days. The A/B-scan ultrasonography indicated that there were clumping echo accompanied with punctiform or short linear echo in vitreous body of groups A, B and C after 7 days ; Mild vitreous opacity was found in group D after 42 days; Point-linear echo was in vitreous body of group E after 7 days to 14 days,which was weaker than that in groups A,B or C at the same time,and no obvious abnormal echo was found after 21 days. With histopathological examination, the structure of eyeball was destroyed in groups A, B and C ; I

关 键 词：细菌性眼内炎 眼感染 去甲万古霉素 聚N-异丙基丙烯酰胺-聚氧化乙烯 纳米粒 缓释给药系统 

分 类 号：R771.1[医药卫生—眼科]