Antifungal Denture Adhesive Film for Oral Candidiasis

Gerding, Thomas

Abstract

The overall goal of this project is to investigate the feasibility of a novel technology to produce an """"""""Antifungal Denture Adhesive Film"""""""" (ADA) System that will minimize or eliminate the current shortcomings of oral mucosal treatment modalities for candidiasis in denture patients. A recent study reported that over 75 percent of complete denture wearers exhibit dense C. albicans colonization in the sites covered by the upper or lower dentures. Approximately 65 million people in the U.S. are burdened with at least one fully edentulous arch and denture adhesive sales alone exceed $250 million annually. Current estimates for this subpopulation afflicted with this fungus number 10 to 25 million (U.S.). This health disparity is related not only to age of the subject, but other factors as well, such as low socioeconomic level and immunocompromised individuals. This study will test the hypothesis that novel denture adhesive films containing antifungal agents will improve treatment outcomes of oral candidiasis in denture patients. Our approach in Aim 1 is to formulate and produce preliminary ADA systems containing clotrimazole and nystatin. Previous studies will be used to direct the formulation and hot-melt extrusion of the preliminary formulations.
Specific Aim 2 will utilize analytical, dissolution, bioadhesion and thermal tests to evaluate these preliminary formulations and identify lead ADA systems.
Aims 3 and 4 will produce and further investigate lead formulations by stability studies, in addition to testing these systems for in vitro activity against the Candida species in simulated oral cavity conditions.
Aim 5 will evaluate and finalize two optimal bioadhesive drug delivery systems for each model antifungal drug. Successful completion of the project objectives will provide proof-of-concept for an appropriately designed, stable, Antifungal Denture Adhesive Film System that may be advanced to animal or human studies. An ADA system may be used for primary, prophylaxis or adjunct treatment of oral or pharyngeal candidiasis via controlled-release of the antifungal agent from the polymer matrix. In addition, the bioadhesive matrix serves as a denture adhesive for the subject for use in the interim while the fungal infection is being treated on the denture as well. This ADA system will reduce or eliminate the current shortcomings of systemic and currently available topical therapy for oral and pharyngeal candidiasis in a significant patient population.