Intra-oral delivery system for antifungal release

Background: The placement of removable dental prostheses produces significant changes in the oral environment that may lead to adverse effects on the integrity of the oral tissues. Denture-induced candidosis, caused by candidal infection of the palatal mucosa, is the most frequent complication (40 %) in removable denture wearers. It predominantly affects immunosuppressed and medically compromised patients. In these high-risk patients the oral cavity may provide a source for Candida causing systemic infection. Oral candidosis has become a significant challenge in patients with persisting risk factors and a recurrent need for antifungal treatment. In addition, denture-induced candidosis is a mixed biofilm infection which provides multiple challenges for its management. Moreover, the persistent fungal colonisation on the fitting surfaces of denture often leads to cross infection and recurrence of mucosal lesions. These considerations highlight the clear need for new effective antifungal treatment modalities.Aims: The aims of this project were to establish a polymeric delivery device based on denture base lining polymer, poly (ethyl methacrylate) and tetrahydrofurfuryl methacrylate (PEM/THFM), for sustained delivery of antifungal agents [chlorhexidine (CHX) and fluconazole (FLU)], for the use in the treatment of denture-induced candidosis and to test the serviceability of the lining under investigation.Methods: A broth microdilution method was used to assess the spectrum of activity of the antifungal agents (CHX powder and FLU powder in two formulations pure and from capsules) against wide range of Candida species. Bioassay method and spectrophotometry were used to evaluate the efficiency of the PEM/THFM denture liner to release the impregnated antifungal agents and to quantify the released concentrations. Bioassay, time-kill studies and biofilm assays were used to verify the antifungal activity of the released antifungal agents. Shear bond test, water absorption, colorimetery and Fourier Transform Infrared Spectroscopy were used to test clinically important physical and mechanical properties for the impregnated liner.Results: It was found that CHX has broad-spectrum antifungal activity also among Candida species highly resistant to FLU. Both CHX and FLU became readily leached from PEM/THFM polymer up to 4 weeks in microbiologically effective concentrations. CHX demonstrated superior antifungal efficacy against planktonic and biofilm lifestyle of Candida compared to FLU. Findings show that the impregnation with antifungal agents has affected all tested properties (shear bond strength, water absorption, degree of conversion and colour stability) but these changes are comparable to other long-term lining materials and are within acceptable ranges.Conclusions: These findings indicate the feasibility of introducing an efficient treatment modality for candidal infections, especially denture-induced candidosis. A polymeric system containing CHX or FLU could assume a very promising treatment option as the drug is effective and directed to the site of pathology. Moreover, the distinct efficacy of CHX against C. albicans biofilms is a promising outcome to overcome the side effects of conventional antifungal agents and their reduced efficacy against biofilm formation.