Quaternized Thiomers for Antibacterial Activity and Hyperinflammation Mitigation.

Abstract

The surge of infections accompanied by a limited supply of potent antibacterial agents has resulted in an emerging need for broad-spectrum treatments. The ability of superbugs to form resilient biofilms exacerbates the situation. Although natural polymers such as chitosan and its derivatives have been studied for their biocompatibility and antibacterial activity, quaternization and thiolation have been explored separately as distinct modification strategies to enhance their functional performance. However, the synergistic effects of integrating the complementary properties of quaternization and thiolation in the same polymer have not been explored. In this respect, we synthesized quaternary thiolated polymer (QTP) by reacting-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) with thioglycolic acid. QTP shows broad-spectrum activity against drug-resistant Gram-positive and Gram-negative bacteria. The polymer exhibits antioxidant properties that mitigate hyperinflammation while having low in vitro and in vivo toxicity. QTP achieves a significantly reduced bacterial biofilm (>99.9%). When assessed in a superficial wound infection murine model, the polymer not only completely eradicates MRSA burden in vivo but also aids in restoring normal dermal architecture. These findings position QTP as a promising therapeutic candidate for countering resistant bacterial infections.