脂质体包裹环孢素延长大鼠眼角膜移植存活时间

Prolongation of corneal allograft survival with liposome-encapsulated cyclosporine in the rat eye.

作者信息

Milani J K, Pleyer U, Dukes A, Chou H J, Lutz S, Rückert D, Schmidt K H, Mondino B J

机构信息

Jules Stein Eye Institute, University of California, School of Medicine, Los Angeles.

出版信息

Ophthalmology. 1993 Jun;100(6):890-6. doi: 10.1016/s0161-6420(93)31558-7.

DOI:10.1016/s0161-6420(93)31558-7

PMID:8510902

Abstract

PURPOSE

To study the effects of different formulations of topical cyclosporine (Cyclosporin A [CsA]) on corneal allograft rejection in a rat model.

METHODS

Female Lewis rats received penetrating keratoplasties from female Wistar-Furth donors. A total of 78 allogeneic grafts were performed. An additional 15 syngeneic grafts (Lewis) were used as technical controls. Two CsA preparations with equivalent drug concentrations (2.1 mg/ml) were applied as drops: CsA encapsulated in large unilamellar liposomes (CsA-LIP) and CsA dissolved in olive oil (CsA-DR). Allogeneic grafts were randomly assigned to receive CsA-LIP or CsA-DR beginning on the day of surgery five times daily for 10 days. Animals without any treatment or receiving empty liposomes (EM-LIP) were used as treatment controls. Grafts were graded three times weekly and a rejection index was generated based on graft clarity, neovascularization, and vessel size.

RESULTS

All syngeneic grafts remained clear over the observation period of 60 days. Rejected allogeneic grafts without any treatment and those receiving EM-LIP or CsA-DR showed a mean survival time (+/- standard deviation) of 14 +/- 4, 14 +/- 5, and 14 +/- 4 days, respectively. There was no significant difference in mean survival time between the grafts without any treatment and those in CsA-DR or EM-LIP treatment groups. The mean survival time of rejected grafts in animals receiving CsA-LIP was prolonged to 20 +/- 4 days. There was a significant difference in the mean survival time between the CsA-LIP treatment group and groups receiving CsA-DR, EM-LIP, or no treatment (P < or = 0.05). The Kaplan-Meier survival curve of the CsA-LIP treatment group was significantly different from the other experimental groups. The graft survival rate in the CsA-LIP group was 77%, whereas the rate was 37% in the non-treated group, 45% in the CsA-DR group, and 36% in the EM-LIP group.

CONCLUSION

Encapsulation of CsA in liposomes might be a promising formulation for use in the prevention of corneal graft rejection.

摘要

目的

在大鼠模型中研究不同剂型的局部用环孢素（环孢素A [CsA]）对角膜移植排斥反应的影响。

方法

雌性Lewis大鼠接受来自雌性Wistar-Furth供体的穿透性角膜移植术。共进行了78次同种异体移植。另外15次同基因移植（Lewis）用作技术对照。两种药物浓度相等（2.1 mg/ml）的CsA制剂以滴眼剂形式应用：包裹于大单室脂质体中的CsA（CsA-LIP）和溶于橄榄油中的CsA（CsA-DR）。同种异体移植从手术当天开始随机分配接受CsA-LIP或CsA-DR，每天5次，共10天。未接受任何治疗或接受空脂质体（EM-LIP）的动物用作治疗对照。每周对移植片进行3次评分，并根据移植片的清晰度、新生血管形成和血管大小生成排斥指数。

结果

在60天的观察期内，所有同基因移植片均保持清晰。未接受任何治疗的排斥同种异体移植片以及接受EM-LIP或CsA-DR的移植片的平均存活时间（±标准差）分别为14±4天、14±5天和14±4天。未接受任何治疗的移植片与CsA-DR或EM-LIP治疗组的移植片在平均存活时间上无显著差异。接受CsA-LIP的动物中排斥移植片的平均存活时间延长至20±4天。CsA-LIP治疗组与接受CsA-DR、EM-LIP或未治疗组在平均存活时间上有显著差异（P≤0.05）。CsA-LIP治疗组的Kaplan-Meier存活曲线与其他实验组显著不同。CsA-LIP组的移植片存活率为77%，而未治疗组为37%，CsA-DR组为45%，EM-LIP组为36%。