A new form of intraoral delivery of antifungal drugs for the treatment of denture-induced oral candidosis

Abstract

Objectives: To monitor the release of the antifungal drugs Fluconazole, Chlorhexidine and a combination of the two from an auto-polymerized poly (methyl methacrylate) (PMMA) denture base resin; and to investigate the effect of the released drugs upon the growth of Candida albicans.

Methods: A high performance liquid chromatography-Ultra violet (HPLC-UV) method was used in the analysis of the released drugs into distilled water from PMMA discs doped with the antifungal drugs Fluconazole (10%), Chlorhexidine (10%) and a combination of the two drugs (5% each). The antifungal efficacy of the released drugs was monitored, microbiologically, employing "well" technique on a Saborauds culture medium inoculated with a resistant strain of Candida albicans.

Results: It was shown that Fluconazole, Chlorhexidine and the combination of the two drugs can be successfully incorporated with PMMA. It was found that the drugs leach steadily out of the PMMA resin into distilled water at mouth temperature and that sustained drug release continued throughout the 28 days test period. It was also shown that the released drugs demonstrated an antifungal activity against the resistant Candida albicans and this was most remarkable in the combined drugs samples.

Conclusions: The findings of this investigation have a clinical value in terms of their significant contribution to the treatment of fungal infections of the oral cavity. The sustained release of anti-fungal drugs from the PMMA resin clearly constitutes a new dosage form of these drugs via the poly (methyl methacrylate) delivery system.

Keywords: Antifungal drug; Auto-polymerized PMMA; Candida albicans; Chlorhexidine; Denture stomatitis; Eluates; Fluconazole; HPLC-UV; Synergism.

Figure 1

Discs of the three sample groups showing the drug release device (DRD) impregnated with 10% Fluconazole; 10% Chlorhexidine, and with a combination of 5% of each drug.

Figure 2

The High Performance Liquid Chromatography (HPLC) apparatus employed in the present investigation.

Figure 3

A representative chromatogram of a standard mixture of Fluconazole with the internal standard.

Figure 4

A representative chromatogram of a standard mixture of Chlorhexidine with the internal standard.

Figure 5

A representative chromatogram of a standard mixture combining Fluconazole and Chlorhexidine.

Figure 6

Line diagram plotting the cumulative drug conc (μg/ ml) versus time (days) for FNZ, CHX, and FNZ+CHX combination, demonstrating the sustained release of the drugs over the four weeks test period.

Figure 7

Saborauds culture medium inoculated with Candida albicans. Note the three wells prepared to accommodate the eluates from Fluconazole (10%), Chlorhexidine (10%), and the combination drug (5% Fluconazole + 5% Chlorhexidine) discs soaked in distilled water at mouth temperature.

Figure 8

Demonstrating the zone of inhibition of the Candida albicans growth around the well that contained the DRD with 10% Fluconazole antifungal drug. Note the absence of an inhibition zone around the well that contained the control, i.e., the DRD alone.

Figure 9

Demonstrating the zone of inhibition of the Candida albicans growth around the well that contained the DRD with 10% Chlorhexidine antifungal drug. Note the absence of an inhibition zone around the well that contained the control, i.e., the DRD alone.

Figure 10

Demonstrating a remarkably wide zone of inhibition of the Candida albicans growth around the well that contained the DRD with combined antifungal drugs, 5% Fluconazole and 5% Chlorhexidine. Note the absence of an inhibition zone around the well that contained the control, i.e., the DRD alone.

Figure 11

Comparing the zones of inhibition of the Candida albicans growth around the wells that contained the antifungal drugs. Note the remarkably wide inhibition and dilution zones around the well accommodating the combined Fluconazole and Chlorhexidine indicating a synergistic effect of the two antifungal drugs.

Figure 12

A histogram plotting the width of the inhibition zones of the Candidal growth affected by Fluconazole, Chlorhexidine, and the combination of the two antifungal drugs over the four weeks test period.