Tissue response in animal model of tissue conditioner containing inclusion complex antifungal:²-cyclodextrin for denture stomatitis treatment

Abstract

The incorporation of antifungal agents into temporary resilient materials for removable dentures may be an alternative to denture stomatitis' treatment because of breaking the cycle of supporting tissues reinfection via prosthesis, acting on them through the incorporated drugs, which are released gradually over the life cycle of these materials. As this protocol may interfere with the properties of the modified polymer matrix, minimum inhibitory concentrations (MICs) were determined for nystatin (Nys) and chlorhexidine (Clx), which were effective in inactivating the C. albicans biofilm and, simultaneously, resulted in no deleterious effects to the temporary resilient materials throughout their useful life. However, even the release of these antifungal agents occurring in the system directly to the infection site, they may result in a certain degree of toxicity and/or drug interactions and, to reduce such effects it has been suggested the formation of inclusion complexes of drugs with cyclodextrins. At the same time, in a controlled release drug delivery system using acrylic resin-based resilient liners, the cytotoxic effects caused by the soluble substances released by these materials should be considered. It has been shown that the use of acrylic intraoral devices (IODs) containing temporary resilient liner modified by the MIC of ketoconazole caused a significant reduction of the keratin layer of the palate of healthy rats, but the histopathological changes resulting from these materials modified or not by drugs on supporting tissues affected by denture stomatitis are still unknown. During this infectious process, clinically, the supporting tissues of the acrylic bases of removable dentures are altered by epithelial degradation and tissue invasion by fungi. Thus, the objective of this study will be to evaluate, in an animal model, the tissue response after denture stomatitis induction and the use of IOD relined with tissue conditioner modified by drugs at MICs for biofilm of C. albicans tested in their free forms or complexed with ²-cyclodextrin. After denture stomatitis induction (or no - positive control) with the use of IODs contaminated with C. albicans for 4 days, the rats (n = 42) will have their devices sterilized and relined or not by Softone without or with Nys or Clx at MICs in their free or complexed forms. After 7 days of treatment, the animals will be euthanized and the palatal region between molars subjected to the following analyzes: histopathological qualitative analysis by description and histopathological quantitative analysis by computerized planimetry, collagen fiber morphology (birefringence analysis), marker expression of cell proliferation (PCNA), detection of apoptosis at cellular level (TUNEL), immunohistochemical of cytokine expression (L-1² and TNF-±), activities of the myeloperoxidase (MPO) and N-acetyl-²-D-glycosaminidase (NAG) enzymes. The quantitative data will be statistically analyzed (±=0.05) and compared to the qualitative data. (AU)