Effects of three penetration enhancers on transcorneal permeation of cyclosporine

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 Crem ophor-EL. Methods. Human corneas, unsuitable for transplantation, were eith er freshly used for permeability experiments or snap-frozen in Liquid nitro gen and stored at -85 degreesC. CsA permeation through either fresh or thaw ed frozen corneal tissue was determined using a flow-through diffusion appa ratus (20 degreesC for 24 hours). Flux rates for CsA were determined in the presence and absence of the penetration enhancers 0.01% BZCl, 20% DMSO, an d Cremophor-EL (10% and 20%). Analysis of variance and Duncan's multiple-ra nge 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 difference s 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, statisticall y 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 sta tistically significant increases in flux values could be detected. Conclusi ons, 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 dif ferent.