Nonimmunogenic Hydrogel-Mediated Delivery of Antibiotics Outperforms Clinically Used Formulations in Mitigating Wound Infections

Abstract

Treatment of chronic wound infections caused by Gram-positive bacteria such as <i>Staphylococcus aureus</i> is highly challenging due to the low efficacy of existing formulations, thereby leading to drug resistance. Herein, we present the synthesis of a nonimmunogenic cholic acid-glycine-glycine conjugate (<b>A6</b>) that self-assembles into a supramolecular viscoelastic hydrogel (<b>A6</b> gel) suitable for topical applications. The <b>A6</b> hydrogel can entrap different antibiotics with high efficacy without compromising its viscoelastic behavior. Activities against different bacterial species using a disc diffusion assay demonstrated the antimicrobial effect of the ciprofloxacin-loaded <b>A6</b> hydrogel (CPF-Gel). Immune profiling and gene expression studies after the application of the <b>A6</b> gel to mice confirmed its nonimmunogenic nature to host tissues. We further demonstrated that topical application of CPF-Gel clears <i>S. aureus</i>-mediated wound infections more effectively than clinically used formulations. Therefore, cholic acid-derived hydrogels are an efficacious matrix for topical delivery of antibiotics and should be explored further.