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Effects of three penetration enhancers on transcorneal permeation of cyclosporine.

机译:三种渗透促进剂对环孢菌素透角膜渗透的影响。

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PURPOSE: To investigate the permeation of cyclosporin A (CsA) through fresh and frozen human corneas in the presence and absence of three penetration enhancers: benzalkonium chloride (BZCl), dimethylsulfoxide (DMSO), and Cremophor-EL. METHODS: Human corneas, unsuitable for transplantation, were either freshly used for permeability experiments or snap-frozen in liquid nitrogen and stored at -85 degrees C. CsA permeation through either fresh or thawed frozen corneal tissue was determined using a flow-through diffusion apparatus (20 degrees C for 24 hours). Flux rates for CsA were determined in the presence and absence of the penetration enhancers 0.01% BZCl, 20% DMSO, and Cremophor-EL (10% and 20%). Analysis of variance and Duncan's multiple-range test were used to test for steady state, and an unpaired Student t test with Welch's correction was used to test for differences between the mean flux values at each time point. A significance level of 5% was used for all of the statistical tests. RESULTS: No statistically significant differences in flux values of CsA could be detected between fresh and frozen corneas. In the presence of Cremophor-EL (10% and 20%) and 0.01% BZCl, statistically significant increases in flux values of CsA before 16 hours and after 16 hours, respectively, could be observed. In the presence of 20% DMSO, no statistically significant increases in flux values could be detected. CONCLUSIONS: The permeation of CsA through human corneas appeared to be enhanced by the presence of BZCl and Cremophor-EL. Additionally, it was shown that the flux rate of CsA across fresh and frozen corneas was not significantly different.
机译:目的:研究在存在和不存在三种渗透促进剂:苯扎氯铵(BZCl),二甲基亚砜(DMSO)和Cremophor-EL的情况下,环孢菌素A(CsA)通过新鲜和冷冻的人角膜的渗透性。方法:将不适合移植的人角膜新鲜用于渗透性实验或在液氮中速冻并储存在-85摄氏度下。使用流通式扩散装置测定通过新鲜或解冻的冷冻角膜组织的CsA渗透率(20摄氏度,持续24小时)。在存在和不存在渗透促进剂0.01%BZCl,20%DMSO和Cremophor-EL(10%和20%)的情况下,确定CsA的助焊剂率。方差分析和邓肯多范围检验用于检验稳态,而未配对的带Welch校正的Student t检验用于检验每个时间点的平均通量值之间的差异。所有统计检验的显着性水平为5%。结果:新鲜和冷冻角膜之间的CsA通量值在统计学上没有显着差异。在存在Cremophor-EL(10%和20%)和0.01%BZCl的情况下,可以分别观察到在16小时之前和16小时之后,CsA的通量值在统计学上显着增加。在20%DMSO存在下,无法检测到通量值的统计显着增加。结论:BZCl和Cremophor-EL的存在增强了CsA通过人角膜的渗透。另外,表明新鲜和冷冻角膜中CsA的通量率没有显着差异。

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