Drug delivery with fewer fouls: localized antibiotic release and reduced surface biofouling with glutathione-conjugated hydrogels.

Systemic antibiotics are the standard of care for acute bacterial skin and skin structure infections (ABSSSI), but low drug perfusion at the site of infection and higher rates of antibiotic resistance necessitate alternative strategies to enhance local antibiotic concentrations. Wound dressings provide a convenient approach to antibiotic delivery but are limited by fixed, pre-loaded antibiotic concentrations. We have recently demonstrated the use of glutathione-conjugated poly(ethylene glycol) [GSH-PEG] hydrogels for the loading and release of charge-bearing therapeutic molecules. Herein, we evaluate the antibacterial and antibiofilm activities of rationally selected therapeutics released from GSH-PEG hydrogels. Antibiotics released from GSH-PEG hydrogels inhibited the growth of Pseudomonas aeruginosa and Staphylococcus aureus and effectively reduced biofilm formation without significantly influencing human dermal fibroblast proliferation and migration. In addition to controlled antibiotic delivery, GSH-conjugated hydrogels demonstrated markedly lower albumin and bacterial adsorption as compared to unconjugated hydrogels and a traditional wound dressing. The zwitterionic GSH ligands within hydrogels permit selective therapeutic delivery while reducing biofouling, highlighting the GSH-PEG hydrogel platform as a promising candidate for use as a wound dressing material.