P van der Bijl1, A D van Eyk, D Meyer. 1. Department of Pharmacology, Faculty of Medicine, University of Stellenbosch, Tygerberg Medical School, Tygerberg, South Africa.
Abstract
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.
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.
Authors: Arthur Shedden; Ingrid A Adamsons; Albert J Getson; Jean K Laurence; Christopher R Lines; David J Hewitt; Tony W Ho Journal: Graefes Arch Clin Exp Ophthalmol Date: 2010-05-02 Impact factor: 3.117