Tissue response in a rat model of denture stomatitis treated with tissue conditioner containing antifungal complexed with β-cyclodextrin

<b>Introduction.</b> Tissue conditioners modified with antifungals are a potential alternative to denture stomatitis (DS) treatment.<b>Gap Statement.</b> Information on tissue response to this treatment before its clinical application is lacking.<b>Aim.</b> This study aimed to evaluate the tissue response of a tissue conditioner modified with antifungals in a rat model of DS.<b>Methodology.</b> After DS induction for 4 days under antibiotic therapy, Wistar rats had their intraoral devices (IODs) relined with the tissue conditioner Softone without (Soft) or with the MICs against <i>Candida albicans</i> of nystatin (Nys) or chlorhexidine (Chx) complexed or not with β-cyclodextrin (Nys:βCD and Chx:βCD). Three controls were included: healthy rats [negative control (Nc)], rats using a sterile IOD [sterile device (Sd)] and rats with DS that did not receive treatment (DS). After 4 days of treatment, the palatal mucosa under the IODs underwent histological processing for morphohistopathological and histometric analyses, morphology of collagen fibres (birefringence), immunohistochemistry for the expression of cell proliferation (proliferating cell nuclear antigen) and cytokine (IL-1β).<b>Results.</b> The Nc and Sd groups were similar (<i>P</i>>0.05), displaying epithelial and connective tissues without any discernible changes in the parameters assessed. The DS and Soft groups exhibited pronounced epithelial alterations, cell proliferation and expression of the cytokine IL-1β. In groups treated with drug incorporation (Nys, Chx, Nys:βCD and Chx:βCD), all samples demonstrated a reduction in tissue inflammation or complete tissue recovery, with an epithelium compatible with health. For the immunohistochemical parameters, the Chx, Nys:βCD and Chx:βCD groups were comparable with Nc (<i>P</i>>0.05).<b>Conclusion.</b> The proposed treatment could be promising for DS, as it led to the tissue recovery of the palatal mucosa. Nevertheless, much lower concentrations of complexed antifungals were required to achieve a similar or higher degree of tissue response compared with uncomplexed drugs in a modified tissue conditioner formulation.