Polymeric prodrugs of ampicillin as antibacterial coatings

Abstract

A novel ampicillin prodrug containing two carboxylic acid functionalities was synthesized by reacting ampicillin with acyl chloride in the presence of base. This prodrug was subsequently converted into a poly(anhydride-amide) via solution polymerization. The polymer, which chemically incorporates the ampicillin prodrug into the polymeric backbone, was developed as a film to prevent infections associated with medical devices by controlled, localized release of antimicrobials. The robust polymer coatings exhibiting strong adhesion to stainless steel were produced under elevated temperature and reduced pressure. The in vitro hydrolytic degradation of the polymer into the ampicillin prodrug was measured and the antibacterial activity of polymer-derived coatings was examined using a Gram-positive bacterium, Staphylococcus aureus. Furthermore, the polymer cytotoxicity was screened using fibroblasts. The ampicillin prodrug demonstrated antibacterial activity and the polymer demonstrated no cytotoxic effects on fibroblasts. Based on these results, the biodegradation of the antimicrobial-based poly(anhydride-amide) into the prodrug displays substantial promise as an implant or implant coating to reduce device failure resulting from bacterial infections.