Physical properties and cytotoxicity of antimicrobial dental resin adhesives containing dimethacrylate oligomers of Ciprofloxacin and Metronidazole.

OBJECTIVE: Antimicrobial oligomers synthesized from ciprofloxacin (CF) and metronidazole (MN) were investigated for their potential use in dental adhesives. METHODS: Susceptibility of the cariogenic bacterium Streptococcus mutans UA159 to CF, MN, and CF/MN combination was evaluated. Hydrolytic stability and drug release from the oligomers was studied in buffer and simulated human salivary esterase conditions. Cytotoxicity of films with 15wt% drug oligomers co-polymerized with commercial monomers were assessed using human gingival fibroblasts (HGFs). In-house adhesives were prepared and characterized for viscosity. Polymerized films were analysed for gel content and water swelling. Interfacial fracture toughness (KIC) of composites bonded to dentin by either a 2 or 3-step etch-and-rinse approach using the in-house formulated adhesives was measured. RESULTS: The respective minimum inhibitory concentration for CF and MN against S. mutans was 0.7 and 2400µg/mL, with the combination having an additive effect (0.35µg/mL CF with 1200µg/mL MN). Antibiotics were released upon hydrolysis of the oligomers. Films containing the drug oligomers were not cytotoxic against HGFs. Replacing 2-hydroxyethyl methacrylate with the drug oligomers increased the viscosity of the experimental adhesives, reduced gel content, and decreased swelling of films in water. Antimicrobial adhesives demonstrated bonding to dentin with interfacial KIC values comparable to the in-house control in the 2-step application, and with slightly lower KIC values in the 3-step approach. SIGNIFICANCE: The antimicrobial oligomers can be incorporated into dental adhesive systems using formulations that show comparable fracture toughness to commercial materials, and may provide a means to deliver local antimicrobial drug release at the marginal interface.

Synthesis and characterization of Ciprofloxacin-containing divinyl oligomers and assessment of their biodegradation in simulated salivary esterase.

OBJECTIVE: Two leading causes contributing to dental restoration replacement are the marginal breakdown at the composite/dentin interface and secondary caries mediated by bacteria. The objective of the present study was to synthesize oligomers which incorporated enhanced bio-stability but would also be able to generate antimicrobial function if they underwent degradation. METHODS: Stability was incorporated into the oligomers by generating structural features that would physically hinder the availability of hydrolytically sensitive groups in the oligomers. As a proof-of concept for the antibacterial feature, antimicrobial function was achieved by covalently incorporating Ciprofloxacin (CF) into the backbone of cross-linking divinyl oligomers (referred to as EDV and HLH-CFPEG). The hydrolytic stability of the oligomers was studied in simulated human salivary esterase and compared to the commercial monomer 2,2-bis[4(2-hydroxy-3-methacryloxypropoxy)-phenyl]propane (BisGMA). RESULTS: Both drug oligomers were found to be significantly more stable than BisGMA. Upon degradation, both drug oligomers released CF differentially in free form. Polymer synthesis from resin formulations containing 15wt% HLH-CFPEG showed a high degree of vinyl group conversion and gel content, and under hydrolytic conditions showed the release of CF during a 28-day monitoring study period. SIGNIFICANCE: HLH-CFPEG can be used in dental resin adhesive systems for local delivery of CF to the marginal interface. Minimizing the growth of Streptococcus mutans at the marginal site can improve longevity by reducing esterase activity derived specifically from S. mutans.