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[玻璃体内持续递送两性霉素B给药系统对实验性白色念珠菌性兔真菌性眼内炎的抗感染作用]

[Anti-infectious effect of sustained antravitreal amphotericin B drug delivery system on experimental rabbit fungal endophthalmitis of Candida albicans].

作者信息

Chen Nan, Yang Yi-tao, Dong Xiao-guang, Xie Li-xin, Wang Shen-guo

机构信息

State Key Lab Cultivation Base, Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao 266071, China.

出版信息

Zhonghua Yan Ke Za Zhi. 2006 May;42(5):420-5.

PMID:16762236
Abstract

OBJECTIVE

To evaluate the efficacy and toxicity of sustained intravitreal amphotericin B drug delivery system (DDS) on experimental rabbit fungal endophthalmitis of Candida albicans.

METHODS

Fifty New Zealand rabbits received central vitrectomy were followed by Candida albicans suspension (10(4) colony forming unit, cfu) injection. Rabbits were grouped randomly into five with ten in each as follows: Group A, endophthalmitis control group; Group B, DDS of vehicle alone; Group C, topical treatment with amphotericin B eyedrop; Group D, 5 microg of amphotericin B intravitreal injection every week for two weeks; Group E, DDS contained 1 mg of amphotericin B. Slit-lamp and indirect-ophthalmoscope were performed at different time for two months and vitreous opacity was compared between each group. The intraocular drug concentration was measured with high performance liquid chromatography (HPLC). Light and electron microscope were conducted to evaluate the toxicity of DDS and the effect of vehicle on intraocular structure. Electroretinography (ERG) was employed to evaluate the function of retina before and after the implantation of DDS.

RESULTS

Endophthalmitis was obviously inhibited in group E while vitreous was still opacity in other groups. The drug concentration in vitreous cavity was stable and remained for two months in group E while rapidly went down two weeks later in group D. No toxic evidence was found in ocular, liver and kidney tissue and retinal ultrastructure was normal. There was no difference in ERG study before and after the DDS was implanted.

CONCLUSIONS

Sustained intravitreal amphotericin B DDS can significantly suppress the formation of fungal colony and inhibit the development of infection with long and stable intraocular drug concentration maintenance. The vehicle and amphotericin B DDS are safe to intraocular structure.

摘要

目的

评价玻璃体内持续释放两性霉素B给药系统(DDS)对实验性白色念珠菌性兔真菌性眼内炎的疗效和毒性。

方法

50只接受了玻璃体切除术的新西兰兔,随后注射白色念珠菌悬液(10⁴菌落形成单位,cfu)。将兔随机分为五组,每组10只,如下:A组,眼内炎对照组;B组,仅含赋形剂的DDS组;C组,两性霉素B滴眼液局部治疗组;D组,每周玻璃体内注射5μg两性霉素B,共两周;E组,含1mg两性霉素B的DDS组。在两个月内的不同时间进行裂隙灯和间接检眼镜检查,并比较各组之间的玻璃体混浊情况。用高效液相色谱法(HPLC)测量眼内药物浓度。进行光镜和电镜检查以评估DDS的毒性以及赋形剂对眼内结构的影响。在植入DDS前后采用视网膜电图(ERG)评估视网膜功能。

结果

E组眼内炎明显受到抑制,而其他组玻璃体仍有混浊。E组玻璃体内药物浓度稳定并维持两个月,而D组两周后药物浓度迅速下降。在眼、肝和肾组织中未发现毒性证据,视网膜超微结构正常。植入DDS前后ERG检查无差异。

结论

玻璃体内持续释放两性霉素B的DDS可显著抑制真菌菌落形成,抑制感染发展,且能长期稳定维持眼内药物浓度。赋形剂和两性霉素B DDS对眼内结构安全。

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