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The natural polyphenol resveratrol (RES) has shown great potential as an antimicrobial, including against microbes associated with vaginal infections. To fully exploit the activities of RES, an all-natural ingredients formulation for RES delivery at vaginal site has been developed, namely liposomes loaded with RES, incorporated into a chitosan hydrogel as secondary vehicle. Although considered non-toxic and safe on their own, the compatibility of the final formulation must be evaluated for its biocompatibility and non-irritancy to the vaginal mucosa. As a preclinical safety assessment, the impact of RES formulation on the tissue viability, the effect on barrier function and cell monolayer integrity, and cytotoxicity were evaluated using the cell-based vaginal tissue model, the EpiVaginal™ tissue. RES liposomes-in-hydrogel formulations neither affected the mitochondrial activity, nor the integrity of the cell monolayer in RES concentration up to 60 µg/mL. Moreover, the barrier function was maintained to a greater extent by RES in formulation, emphasizing the benefits of the delivery system. Additionally, none of the tested formulations expressed an increase in lactate dehydrogenase activity compared to the non-treated tissues. The evaluation of the RES delivery system suggests that it is non-irritant and biocompatible with vaginal tissue in vitro in the RES concentrations considered as therapeutic.

Toxicity Assessment of Resveratrol Liposomes-in-Hydrogel Delivery System by EpiVaginalTM Tissue Model