Antifungal activity, biofilm-controlling effect, and biocompatibility of poly(N-vinyl-2-pyrrolidinone)-grafted denture materials

Abstract

Colonization and biofilm-formation of Candida species on denture surfaces cause Candida-associated denture stomatitis (CADS), a common, recurring disease affecting up to 67% of denture wearers. We developed poly(N-vinyl-2-pyrrolidinone)-grafted denture materials that can be repeatedly recharged with various antifungal drugs to achieve long-term antifungal and biofilm-controlling effects. The monomer, N-vinyl-2-pyrrolidinone (NVP), was grafted onto poly(methyl methacrylate) denture resins through plasma-initiated grafting polymerization. The physical properties and biocompatibility of the resulting resins were not negatively affected by the presence of up to 7.92% of grafted poly (N-vinyl-2-pyrrolidinone) (PNVP). Miconazole and chlorhexidine digluconate (CD) were used as model antifungal drugs. PNVP grafting significantly increased the drug absorption capability of the resulting denture materials. Further, the new materials showed sustained drug release and provided antifungal effects for weeks (in the case of CD) to months (in the case of miconazole). The drug-depleted resins could be recharged with the same or a different class of antifungal drug to further extend antifungal duration. If needed, drugs on the PNVP-grafted denture materials could be “washed out” (quenched) by treating with PNVP aqueous solutions to stop drug release. These results point to great potentials of the new materials in controlling biofilm-formation in a wide range of device-related applications.

Controlling fungal biofilms with functional drug delivery denture biomaterials

“…According to the test method of International Organization for Standardization (ISO) 1567, water sorption and water solubility during storage in water for denture base materials should not exceed 32 mg/mm 3 and 1.6 mg/mm 3 , respectively. [23] Apparently, the new resins grafted with the three types of functional polymers had much lower values (hundreds of times lower; μg/mm 3 vs mg/mm 3 ) than these standards, suggesting that the resins could be candidates of denture materials for real applications.…”

“…These concentrations were higher than the lowest miconazole content on denture materials needed to generate a clear inhibition zone against C. albicans (21.73 ± 2.04 μg/cm 2 ). [23] The sustained release could be attributed to specific interactions formed between the antifungal drug and the functional groups of the grafted polymers, which could form a thin layer of polymer matrix on the resin surfaces to trap the drugs, as well as the low water solubility of miconazole (<1.03 μg/mL). Pristine PMMA control resins, on the other hand, only released a small amount of miconazole at the first three days and did not have any drug to release thereafter due to the low miconazole binding capacity.…”

“…After certain releasing periods, the contents of remaining miconazole on the discs were measured following a previously reported method. [23, 34]…”

“…[23] The resulting denture resins could bind and then slowly release antifungal drugs for months, offering an innovative approach to control CADS. To establish the structure-property relationships of this class of denture materials for further development of the CADS-managing device, in the current study, we designed three classes of functionalized denture materials and investigated the drug binding and drug releasing behaviors as well as the antifungal activities and biofilm-controlling properties of the resulting resins.…”

“…PNVP, PMAA and PHEMA are biocompatible polymers that have been widely used in drug formulations and surface modification of medical devices. [23–30] We found that the three classes of the new, functionalized denture materials had significantly higher drug binding capabilities toward miconazole than the original PMMA denture control resins, leading to sustained drug release and potent biofilm controlling effects against Candida . PNVP-grafted resin showed the highest drug binding capability and the most potent anticandidal effects, demonstrating the importance of specific interactions between functional groups of biomaterials and antifungal drugs on drug binding and drug releasing behaviors for controlled release.…”