玻璃体腔注射伏立康唑缓释微球对兔烟曲霉菌性眼内炎的抗感染作用  

Anti-infectious activity of intravitreal injectable voriconazole microspheres on experimental rabbit fungal endophthalmitis of Aspergillus fumigatus

作　　者：杨丽娜[1] 辛萌[1] 吴祥根[1] 姜皓然[1] 

机构地区：[1]山东省眼科研究所,山东省眼科学重点实验室-省部共建国家重点实验室培育基地,山东青岛266071

出　　处：《药学学报》2010年第6期778-784,共7页Acta Pharmaceutica Sinica

摘　　要：评价玻璃体腔内注射伏立康唑缓释微球(voriconazole microspheres,VCZ-MS)对兔烟曲霉菌性眼内炎的治疗作用,为治疗真菌性眼内炎开辟新途径。制备VCZ-MS并对其理化性质进行考察。采用新西兰大白兔右眼玻璃体腔内注入1×103CFU·mL-1烟曲霉孢子悬液建立烟曲霉菌性眼内炎模型,建模成功的动物随机分为A组(空白对照组)、B组(玻璃体切除联合100μg·0.1mL-1伏立康唑眼内注射)、C组(玻璃体切除联合0.5mg VCZ-MS注射)、D组(玻璃体切除联合1.0mgVCZ-MS注射)和E组(玻璃体切除联合1.5mgVCZ-MS注射)。术后不同时间点观察前房闪辉、房水细胞及玻璃体混浊程度,评价治疗效果,并进行组织病理学检查。制备的微球球形圆整,微球载药量和包封率分别为29.94%和73.5%,具有显著的体外缓释特性。药效结果表明,A组眼内炎发生率为100%,迅速发展为全眼球炎,导致眼球萎缩。B、C、D、E组炎症反应均较A组轻(P<0.05)。B组玻璃体混浊度较C、D、E组重(P<0.05)。C组有2只眼在接种烟曲霉菌后3～5d出现后极部积脓,失去控制。D和E组接种烟曲霉菌后8周,所有炎症控制眼的眼底清晰,无复发。组织病理学结果表明,治愈眼结构正常;炎症未控制眼多萎缩,球壁结构破坏。该研究证实玻璃体腔内注射VCZ-MS明显优于传统制剂玻璃体腔注射给药,玻璃体腔注射VCZ-MS能安全有效地抑制烟曲霉菌性眼内炎的发展,以含伏立康唑1.0mgVCZ-MS较佳。The therapeutic effect of sustained intravitreal injectable voriconazole microspheres（VCZ-MS） on an experimental endophthalmitis of Aspergillus fumigatus was investigated.VCZ-MS was prepared successfully and its physico-chemical property was also evaluated.Right eyes of albino rabbits were infected with an intravitreal injection of 1 000 CFU·mL-1 of susceptible Aspergillus fumigatus.All fungal endophthalmitis models were randomly divided into five groups 48 hours later：Group A is control group with no treatment;in group B,vitrectomy was performed combined with intravitreal 3 times injections of 100 μg·0.1 mL-1 voriconazole every other day.In group C,D and E,vitrectomy was performed combined with intravitreal injection of 0.5 mg,1.0 mg and 1.5 mg VCZ-MS respectively.The treatment effect was assessed by slit lamp and indirect ophthalmoscope funduscopy examination,using clinical grading system of inflammation in the anterior chamber and the vitreous opacity.The optical microscopy revealed that microspheres obtained from the experiment design were opaque,discrete and spherical particles with smooth surfaces.The drug content and encapsulation efficiency of microspheres were 29.94% and 73.5%,respectively.Endophthalmitis occurred in all eyes of group A,and rapidly developed to panophthalmitis.The inflammation grade of group B,C,D or E was lower than that of group A（P 0.05）.The grade of vitreous opacity in group C,D,E is lower than group B（P 0.05）.Two eyes in group C developed to panophthalmitis.But in group D and E,all eyes whose inflammation was controlled had no recurrence with vitreous clear.Histopathological examination showed normal structures in the cured eyes,while most uncured eyes were atrophic and with eyeball destroyed.So,it can be safely concluded that the curative effect of intravitreal VCZ-MS is significantly better than that of routine intraocular injection of voriconazole.The optimal dose is the one containing 1.0 mg voriconazole.

关 键 词：伏立康唑 微球 烟曲霉菌 眼内炎 眼感染 真菌性 

分 类 号：R943[医药卫生—药剂学]