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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。
To evaluate the therapeutic effect of intravitreal injection of voriconazole microspheres (VCZ-MS) on Aspergillus fumigatus endophthalmitis in rabbits and to find a new way to treat fungal endophthalmitis. VCZ-MS was prepared and its physical and chemical properties were investigated. The aspergillus fumigatus endophthalmitis model was established by injecting 1 × 103CFU · mL-1 Aspergillus fumigatus into the vitreous cavity of right eye of New Zealand white rabbits. The model animals were randomly divided into group A (blank control group), group B (Vitrectomy combined with 100μg · 0.1mL-1 voriconazole intraocular injection), group C (vitrectomy combined with 0.5mg VCZ-MS injection), group D (vitrectomy combined with 1.0mgVCZ-MS injection) and group E (vitrectomy combined with 1.5 mg VCZ-MS injection). The anterior chamber glare, aqueous humor and vitreous opacity were observed at different time points after operation to evaluate the therapeutic effect and histopathological examination. The microspheres prepared were spherical round, the drug loading and entrapment efficiency of microspheres were 29.94% and 73.5%, respectively, with significant in vitro release characteristics. Efficacy results show that A group of endophthalmitis incidence of 100%, the rapid development of all-cause inflammation, resulting in atrophy of the eye. Inflammatory reaction in group B, C, D and E were lighter than that in group A (P <0.05). The vitreous turbidity in group B was heavier than those in groups C, D and E (P <0.05). There were 2 eyes in Group C after 3 to 5 days after inoculation with Aspergillus fumigatus, and they lost control. Eight and eight weeks after inoculation with Aspergillus fumigatus in groups D and E, all eyes with inflammation-control eyes had clear-cut eyes without recurrence. Histopathological results showed that the normal structure of the eye to heal; Inflammation uncontrolled eye atrophy, the destruction of the wall structure. The study confirmed that intravitreal injection of VCZ-MS was significantly better than the traditional preparation of vitreous cavity injection, intravitreal VCZ-MS injection can be safe and effective suppression of Aspergillus fumigatus endophthalmitis development to voriconazole 1.0mgVCZ-MS than good.