Permeability of Intact and De-Epithelialised, Human Vaginal Mucosa to Tacrolimus and Cyclosporin A

Abstract

Immunosuppressants may be applied topically to mucosal surfaces for treating inflammatory diseases, e.g. vulvar lichen planus and Behçet's disease. The efficacy of the treatment is dependent on the potency of the drug and its penetration into the tissue. In this study the in vitro diffusion characteristics of Tacrolimus (Tac) and Cyclosporin A (CsA) across human vaginal mucosa are investigated and compared. Fresh human vaginal mucosa was snap-frozen in liquid nitrogen and stored at −85 °C. Prior to an experiment, the tissue was defrosted to 20°C in PBS buffer, pH 7.4, and placed in the seven flow cells of a flow-through perfusion apparatus. Either tritiated Tac, or CsA, was then pipetted into the donor chamber of the flow cell. Samples from each flow cell were collected every 2 hours (1.5 ml/h) over a 24-hour period. Statistical analyses were carried out using an F-test. CsA and Tac flux values progressively increased throughout the 24-hour period, and steady state was not reached for either drug. The mean estimated flux values (mean at 16, 20 and 24 h) for Tac (599 ± 44 dpm.cm −2 .min −1 ) were greater than those for CsA (96 ± 5.0 dpm. cm −2 .min −1 ). Whole curve comparison indicated statistically significant differences (P = 1.77×10 −163 ). Both drugs diffuse well across vaginal mucosa. However, mean steady state flux values for Tac were approximately 6 times higher than those for CsA, indicating that human vaginal mucosa is less permeable to CsA than to Tac.