Diffusion rates of vasopressin through human vaginal and buccal mucosa

Abstract

The permeability to several chemical compounds and the histology of vaginal and buccal mucosa are very similar. Because vaginal mucosa is more abundant, it may be used as a model for the latter. To further develop the vaginal/buccal mucosa model, the objective of the present study was to evaluate the passage of a small polypeptide, vasopressin, across fresh and frozen specimens of these two mucosae. Specimens of fresh buccal and vaginal mucosa were taken from excised tissue obtained following vaginal hysterectomies and various oral surgical procedures. Pieces of buccal and vaginal tissue specimens obtained were used fresh or were snap-frozen and stored at -85 degrees C for periods of up to 10 months. Biopsies from fresh and thawed specimens were mounted in flow-through diffusion cells and their permeability to tritiated vasopressin was determined using a continuous flow-through perfusion system. Specimens were examined histologically before and after freezing as well as before and after permeability experiments and similarities between vaginal and buccal tissues verified. No statistically significant differences between flux values for fresh and frozen vaginal and buccal mucosa, respectively, were found. These results demonstrate that the permeation of vasopressin across fresh and frozen human vaginal and buccal mucosa is for practical purposes similar. These results further support the human vaginal/buccal mucosa model for in vitro permeability studies on therapeutically active compounds.

Porcine buccal mucosa as in vitro model: Effect of biological and experimental variables

“…Buccal mucosa wrapped in aluminum foil and frozen at −20°C for 3 weeks was found to have the same fentanyl permeability when compared with fresh mucosa 32. Similar results were reported with other drugs where the permeability did not alter after freezing the buccal mucosa at −20°C 38–40. Again the thickness of the buccal tissue might be the plausible explanation for the difference in the findings.…”

Development and Evaluation of an In Vitro Vaginal Model for Assessment of Drug’s Biopharmaceutical Properties: Curcumin

“…Although this route offers a gender-specific treatment of systemic or local, female-related conditions (2,3), the merits of vaginal administration such as the avoidance of hurdles associated with per-oral or parenteral application (i.e., drug hepatotoxicity, first-pass drug metabolism, drug plasma concentrations fluctuations, side effects, inconvenience, irritation of gastrointestinal mucosa; 2) enable prolonged dosing with lower daily doses of drugs applied in controlled-release delivery systems (1). Achieving comparable pharmacodynamic effects by vaginal route as by per-oral drug delivery provides indirect proof of effective drug absorption through vaginal mucosa owing to its high absorptive surface area, rich blood supply, significantly diminished expression of phase I and II metabolizing enzymes and transporters, and sufficient permeability to drugs (4)(5)(6)(7)(8)(9)(10).…”

Permeability of tritiated water through human cervical and vaginal tissue

“…Currently, hormone replacement and contraceptive products administered vaginally are available in the market. It has been shown that systemic effects are observed with these products when administered intravaginally 7–29. Given this information combined with the data presented, the importance of studying the potential for systemic uptake of drugs by these mucosa must be evaluated for development of safe and effective vaginal drug delivery systems.…”

“…However, it is challenging to define the best freezing technique that will preserve the permeability pathways in the tissue. In studies conducted by Van der Bijl et al11–14,18 evaluating the permeability of tritiated water through buccal and vaginal mucosa, it was shown that freezing at −85°C did not alter water permeability. No studies have been conducted with human cervical tissue.…”

“…Samples could then be thawed immediately before permeability studies. Several methods have been reported for storing human specimens 13–19. However, it is challenging to define the best freezing technique that will preserve the permeability pathways in the tissue.…”