(718h) 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.