Controlled Release of Usnic Acid from Biodegradable Polyesters to Inhibit Biofilm Formation

Controlled and sustained release of antibacterial drugs is a promising approach to address challenges related to bacterial infections in biomedical implants. Biocompatible polyols like xylitol and mannitol are frequently used to synthesize cross-linked, biodegradable polyesters. Xylitol-based adipoyl and sebacoyl polyesters were synthesized by a catalyst free melt polyesterification technique. Unlike traditional drug delivery systems, the objective of this work was to develop biodegradable polymers with usnic acid (UA), a known antibacterial agent, entrapped in the polymer network. Apart from offering a wider control of the release kinetics and improved processability, the hydrolytic degradation results in the concomitant resorption of the polymer. Polymer properties such as degradation, modulus, and drug release were tuned through a subtle change in the chain length of the diacid. In 1 week, the xylitol based adipoyl ester degrades 41% and releases 25% of its initial drug loading whereas the sebacoyl ester degrades 23% in and releases 9% of the loaded drug. A kinetic model has been used to understand the UA release profiles and determine degradation and release parameters that influence release from the polymers. These polyesters are cytocompatible and exhibit excellent bactericidal activity against Staphyloccus aureus by inducing oxidative stress. This work enables a strategy to synthesize biodegradable polymers for potential to inhibit biofilm formation in vivo with tunable mechanical and degradation properties, and variable controlled release.