Synthesis and Characterization of An Antibiotic Hydrogel Wound Dressing Containing Covalently-Linked Vancomycin

While localized antibiotic therapy is a logical solution for treating surgical infection sites, if the delivery matrix is depleted of antibiotics, the resulting empty polymer becomes an ideal structure for harboring the growth of bacterial biofilms. As such, the exact tuning of release with dose and residence time of the depot matrix is required to avoid this mode of infection re-emergence. One method to match release with polymer degradation is the covalent incorporation of the drug into the backbone structure of the polymer. Antibiotics that contain primary or secondary amines can be readily incorporated into a poly(beta-amino ester) (PBAE) polymer via Michael-Addition reaction. However, the degradation product will be a new chemical entity, requiring reevaluation of function and structure. In this work, we evaluated vancomycin incorporation into PBAE polymers. Degradation studies were performed and the products of degradation were verified via HPLC and mass spectroscopy. Comparing the hydrogel degradation profile to that of vancomycin release, the covalently-linked vancomycin had a reduction in burst release and followed the degradation trend more closely than the freely-loaded system. Through variation of hydrophobic:hydrophilic content of the hydrogels, degradation rates were achieved between five days and three weeks. This degradation translated to vancomycin release rates between five days and three weeks, respectively, which was contrary to the freely-loaded system which exhausted their payload up to ten days earlier for the same degradation period. Kirby-Bauer assays indicated antibacterial activity of vancomycin release products against S. aureus.