Enhancement of transmucosal permeation of cyclosporine by benzalkonium chloride.

ABSTRACT

OBJECTIVES: Permeation of cyclosporin A (CsA) through intact and de-epithelialized human vaginal mucosa in the presence and absence of benzalkonium chloride (BZCl) was tested. MATERIALS AND METHODS: Human vaginal mucosa (snap-frozen in liquid nitrogen, stored at -85 degrees C) had been used for permeability experiments. CsA permeation through thawed frozen intact and de-epithelialized vaginal mucosa was determined using a flow-through diffusion apparatus (20 degrees C, 24 h). Flux rates for CsA across these two mucosae were determined in the presence and absence of 0.01% BZCl. ANOVA and Duncan's multiple range test were used to test for steady-state and an unpaired t-test with Welch's correction was used to test for differences between the mean flux values at each time point (significance level of 5%). A piece of thawed tissue from each patient, before and after de-epithelialization, was placed in formalin and histologically examined. RESULTS: Flux rates of CsA across intact vaginal mucosa tended to increase by 28-46% in the presence of 0.01% BZCl, and CsA across de-epithelialized mucosa by approximately 28%. The latter differences were statistically significantly higher after 10 h. Flux rates across de-epithelialized mucosa were 52-140% higher in the presence of 0.01% BZCl (statistically significantly higher after 12 h). CONCLUSIONS: The permeation of CsA through intact and de-epithelialized human vaginal mucosa can be enhanced by 0.01% BZCl.