Sulfonium-Cross-Linked Hyaluronic Acid-Based Self-Healing Hydrogel: Stimuli-responsive Drug Carrier with Inherent Antibacterial Activity to Counteract Antibiotic-Resistant Bacteria.

Augmentation of the activity of FDA-approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic-resistant bacteria. This study reports the development of sulfonium-cross-linked hyaluronic acid (HA)-based polymer (HA-SS-HA) as an inherent antimicrobial agent and antibiotic carrier. The HA-SS-HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli-responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment. Systematic antibacterial studies revealed that the HA-SS-HA encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restored its activity against the antibiotic-resistant bacterial cells methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococci (VRE), and Pseudomonas aeruginosa. The HA-SS-HA gel showed robust efficacy in eradicating the mature biofilm of Staphylococcus aureus (S. aureus). The membrane-disrupting activity revealed that HA-SS-HA could also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies revealed excellent wound-healing activity of HA-SS-HA in albino laboratory-bred (BALB/c) mice. The outcome of additional antibacterial studies revealed that antibiotics encapsulated HA-SS-HA hydrogel could effectively combat Gram-negative, Gram-positive, and antibiotic-resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA-SS-HA could be considered a valuable and economically effective strategy to fight against antibiotic-resistant bacterial strains. This article is protected by copyright. All rights reserved.