Physicochemical Characteristics of Molecules and Their Diffusion across Human Vaginal Mucosa

The diffusion rate of permeant molecules through mucosal tissue depends on the physicochemical characteristics of the molecules themselves as well as the properties of the tissue. In this study the diffusion kinetics of various molecules was examined through intact as well as de-epithelialised human vaginal mucosa. The molecules studied included tritium-labelled water, 17β-estradiol, reduced-arecoline, vasopressin, oxytocin, bradykinin, tacrolimus, cyclosporin A, dihydro-alprenolol, cimetidine and benzylpenicillin. Freshly harvested human vaginal tissue was frozen in liquid nitrogen and stored at −85°C. A flow-through diffusion apparatus was used for the in vitro permeability studies (24 h, 20°C, 1.5 ml/h). The mean estimated – or mean steady-state flux values for all the molecules studied across intact human vaginal mucosa, were generally found to be lower than those of the corresponding de-epithelialised tissue. Using an F-test and comparing whole curves, statistically significant differences in the diffusion rates of tacrolimus, reduced-arecoline, vasopressin, bradykinin, benzylpenicillin, water and cimetidine were found when comparing intact and de-epithelialised vaginal mucosa. Generally, smaller permeant molecules diffused at a higher rate than larger molecules. The epithelial layer retarded the diffusion rate of molecules carrying charges at physiological pH. Damage to the epithelial layer did not necessarily increase the diffusion rate of all molecules tested and small lipophilic molecules did not necessarily diffuse at higher rates than hydrophilic molecules.