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

Abstract

Augmentation of the activity of Food and Drug Administration‐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 reveal that the HA‐SS‐HA‐encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restore 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 shows robust efficacy in eradicating the mature biofilm of Staphylococcus aureus (S. aureus). The membrane‐disrupting activity reveals that HA‐SS‐HA can also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies reveal excellent wound‐healing activity of HA‐SS‐HA in albino laboratory‐bred (BALB/c) mice. The outcome of additional antibacterial studies reveals that antibiotics‐encapsulated HA‐SS‐HA hydrogel can effectively combat Gram‐negative, Gram‐positive, and antibiotic‐resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA‐SS‐HA can be considered a valuable and economically effective strategy to fight against antibiotic‐resistant bacteria.

Engineering Titanium–Hydroxyapatite Nanocomposite Hydrogels for Enhanced Antibacterial and Wound Healing Efficacy

“…However, the excessive use of antibiotics causes consequential drawbacks, including allergy, toxicity, and bacterial resistance. Importantly, the bacteria and microorganisms at the wound site may develop resistance to commonly used antibiotics. − …”