Abstract
This work reports on polymer-antibiotic conjugates (PACs) as additives to resin-based restorative dental materials as a new strategy to convey sustained antibacterial character to these materials. Such antibacterial performance is expected to improve their longevity in the oral cavity. Using the previously reported ciprofloxacin (Cip)-based PAC as a control, a penicillin V (PV)-based PAC was investigated. The monomer-antibiotic conjugate (MAC) containing a methacrylate monomer group and a PV moiety was prepared via nucleophilic substitution between 2-chloroethyl methacrylate (CEMA) and penicillin V potassium (PVK). The PV-based PAC was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of the MAC with hydroxyethyl methacrylate (HEMA), and further characterized by (1)H NMR and gel permeation chromatography (GPC) analysis. Antibiotic resistance was investigated by passaging bacteria in low concentrations of the antibiotic for 19 days, followed by a 48 h challenge at higher concentrations. Our results suggest that the development of antibiotic resistance is unlikely. Zone of inhibition (ZOI) assays revealed no clearing zones around PV-containing resins indicating minimal antibiotic leakage from the material. Similarly, MTT assay demonstrated that the antibiotic-containing specimens did not release cytotoxic byproducts that may inhibit human gingival fibroblast growth. Counting of colony-forming units in an S. mutans biofilm model was used to assess bacterial survival at baseline and after subjecting the antibiotic-containing resin specimens to an enzymatic challenge for 30 days. Significantly reduced bacterial counts were observed as the biofilm aged from 24 to 72 h, and salivary enzymatic exposure did not reduce the antibacterial efficacy of the discs, suggesting that PV-resin will be effective in reducing the re-incidence of dental caries.