Topically applied cyclosporine in azone prolongs corneal allograft survival.
Topically applied cyclosporine in azone prolongs corneal allograft survival.
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DOI：
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发表时间：
1988-02
影响因子：
4.4
通讯作者：
C. Newton;B. Gebhardt;H. Kaufman
中科院分区：
文献类型：
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作者：
C. Newton;B. Gebhardt;H. Kaufman
本研究的目的是开发和测试免疫抑制药物环孢素的局部眼部给药系统。为此，环孢素被溶解在渗透促进剂氮酮中，并局部应用于同种异体兔眼。用放射免疫法测定治疗兔角膜、房水和血液中环孢素的浓度。通过临床评价、组织病理学和免疫组织学评价环孢素氮酮制剂对同种异体角膜移植存活的影响。在接受治疗的角膜中检测到了临床上显著的环孢素浓度，但在接受治疗的动物的房水或血液中几乎没有发现药物。氮酮应用环孢素可抑制移植物排斥反应的严重程度和发生率。免疫组织学观察证实了对移植物排斥反应的抑制作用。环孢素处理的移植物含有的浸润性T细胞明显少于药物/溶剂处理的同种异体移植物，这表明局部应用环孢素能有效地抑制T细胞进入移植物。这项研究首次提出了一种表面上无毒但在局部应用于角膜后有效地输送免疫活性浓度的环孢素的溶剂。
The purpose of this study was to develop and test a topical ocular delivery system for the immunosuppressive drug cyclosporine. To this end, cyclosporine was dissolved in the penetration enhancer, Azone, and applied topically to allografted rabbit eyes. The concentration of cyclosporine in the cornea, the aqueous humor, and blood of the treated rabbits was determined by radioimmunoassay. The effect of the cyclosporine-Azone preparation on the survival of corneal allografts was assessed by clinical evaluation of the grafts and by histopathologic and immunohistologic evaluation of the cellular infiltrate in the grafts. Clinically significant concentrations of cyclosporine were measured in the treated corneas but little or no drug was found in the aqueous humor or blood of the treated animals. Cyclosporine in Azone resulted in suppression in the severity and incidence of graft rejection. The suppression of graft rejection was borne out by the immunohistologic observations. Cyclosporine-treated grafts contained significantly fewer infiltrating T lymphocytes than did the drug/solvent-treated allografts, indicating that the topical application of cyclosporine actively inhibited the entry of T cells into the grafts. This study, for the first time, presents a solvent that is apparently not toxic but is effective in delivering immunologically active concentrations of cyclosporine following topical application to the cornea.