Yang Xia, Dong Xiao-Guang, Liu Ai-Ming, Sun Shi-Ying, Xie Li-Xin, Wang Shen-Guo
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao 266071, China.
Zhonghua Yan Ke Za Zhi. 2007 Jun;43(6):546-53.
To observe a new amphotericin B drug delivery system (AmB-DDS), and investigate the therapeutic effects of AmB-DDS on an experimental Aspergillus fumigatus endophthalmitis.
(1) In order to observe the effects of AmB-DDS, thirty-four New Zealand albino rabbits were intravitreal injected Aspergillus fumigatus suspension (10(3) colony forming unit, CFU) in applanation of vitreous body before therapy 48 hours. All models were randomly divided into five groups. Group A was the empty control group, treated nothing after Aspergillus fumigatus injection, group B was the empty DDS implantation combined with vitrectomy, no treatment after DDS implanted, group C: AmB 5 microg-injection combined with vitrectomy, the injection was repeated two week later, group D: 250 microg AmB-DDS intravitreal implantation combined with vitrectomy, Group E: 500 microg AmB-DDS intravitreal implantation combined with vitrectomy. Aqueous flare, cells, anterior vitreous cells and vitreous opacity were graded, and vitreous humor smear and culture were performed at different time points after operation in 8 weeks. Two months after operation, light microscopy was used histology evaluation. (2) To observe the release of AmB-DDS in Group H (6 eyes), 500 microg AmB-DDS were implanted in the eye of the rabbits after vitrectomy, vitreous humor was aspirated and the concentrations of amphotericin B were determined by high performance liquid chromatography (HPLC).
The inflammation response was lower in groups C, D, E than groups A, B. There was no significant statistical difference between group A and group B (P > 0.05), but differences among C, D, E and groups A, B were significant (P < or = 0.005). The inflammation grade was lower in group E than group C (P < or = 0.005). There was significant statistical difference between the cure effect of group E and group D (chi(2) = 10.494, P = 0.003). All of vitreous humor smears was positive in 1.5 months after surgery, but the culture was only positive in group A, and B. Pathological examination indicated that normal structure was disappeared in the eyes with Aspergillus endophthalmitis. At the first day after surgery, AmB were observed by analysis of HPLC, there was sustained AmB release in the group of AmB-DDS application during the observation periods.
The degradable AmB-DDS can effectively suppress the inflammation of the rabbit model of Aspergillus fumigatus endophthalmitis. As an alternative to the current routine therapy, it can be used for the treatment of Aspergillus fumigatus endophthalmitis.
观察新型两性霉素B给药系统（AmB-DDS），并研究AmB-DDS对实验性烟曲霉菌性眼内炎的治疗效果。
（1）为观察AmB-DDS的效果，34只新西兰白兔在治疗前48小时经扁平部玻璃体腔内注射烟曲霉菌悬液（10³菌落形成单位，CFU）。所有模型随机分为五组。A组为空对照组，注射烟曲霉菌后未做任何处理；B组为植入空DDS并联合玻璃体切除术，植入DDS后未做处理；C组：玻璃体腔内注射5μg两性霉素B并联合玻璃体切除术，两周后重复注射；D组：玻璃体腔内植入250μg AmB-DDS并联合玻璃体切除术；E组：玻璃体腔内植入500μg AmB-DDS并联合玻璃体切除术。对房水闪光、细胞、前部玻璃体细胞和玻璃体混浊进行分级，并在术后8周的不同时间点进行玻璃体腔涂片和培养。术后两个月，采用光学显微镜进行组织学评估。（2）为观察H组（6只眼）中AmB-DDS的释放情况，玻璃体切除术后将500μg AmB-DDS植入兔眼，抽取玻璃体腔液，采用高效液相色谱法（HPLC）测定两性霉素B的浓度。
C、D、E组的炎症反应低于A、B组。A组和B组之间无显著统计学差异（P>0.05），但C、D、E组与A、B组之间差异显著（P≤0.005）。E组的炎症分级低于C组（P≤0.005）。E组和D组的治疗效果之间存在显著统计学差异（χ²=10.494，P=0.003）。术后1.5个月所有玻璃体腔涂片均为阳性，但培养仅在A组和B组为阳性。病理检查表明，烟曲霉菌性眼内炎的眼中正常结构消失。术后第一天，通过HPLC分析观察到两性霉素B，在应用AmB-DDS的组中观察期内两性霉素B持续释放。
可降解的AmB-DDS能有效抑制烟曲霉菌性眼内炎兔模型的炎症。作为当前常规治疗的替代方法，它可用于治疗烟曲霉菌性眼内炎。
