Effect of temperature on permeability of mucosa to water.
In previous studies it has been demonstrated that frozen human vaginal mucosa can be used as a model of buccal mucosa for in vitro permeability studies on a variety of chemical compounds, including drugs. However, most of the latter studies have, for the sake of convenience, been conducted at room temperature (+/- 20 degrees C). The objective of the present study was to determine the effects of increased temperature on steady state flux rates of water through vaginal mucosa. Specimens of clinically healthy human vaginal mucosa were obtained from excess tissue removed during a vaginal hysterectomy from a single patient, snap-frozen in liquid nitrogen at -85 degrees C and banked for 8 months. After thawing in PBS buffer, seven sections from the vaginal mucosa were mounted in flow-through diffusion cells (exposed area 0.039 cm2) and their permeability to tritiated water determined using a continuous flow-through perfusion system at temperatures of 25 degrees, 30 degrees and 37 degrees C. Permeability experiments were performed in triplicate at each temperature setting. Specimens were examined histologically before and after permeability experiments. Mean water flux rates at steady state (16-24 h) were found to be 1760 +/- 22 SEM, 2623 +/- 63 SEM and 4155 +/- 70 SEM cpm. cm-2.min-1, at temperatures of 25 degrees, 30 degrees and 37 degrees C, respectively. A linear regression analysis and plot (r2 = 0.99) displayed a slope of 200 +/- 13 SEM cpm. cm-2.min-1/degree C. The results of this study clearly demonstrated the temperature-dependency of flux rates of water across vaginal mucosa, and this should be taken into account whenever the in vitro vaginal/buccal model is used at room temperature for predicting in vivo buccal drug absorption kinetics.