Combating antimicrobial resistance: In vitro and in vivo efficacy of berberine-loaded metal-organic frameworks with hyaluronic acid coating
Afsoun Mansouri, Nasim Kaveh Farsani, Alireza Javanmard, Mohammadmahdi Eskandarisani, Shekoufe Mohebbi, Mohammadreza Tajik, Somayeh Sadeghi, Faten Eshrati Yeganeh, Hassan Noorbazargan
Abstract
To create a new antimicrobial delivery system, we synthesized UiO-66-NH₂ (UN) metal-organic frameworks (MOF) loaded with berberine (UNB) and coated with hyaluronic acid (UNB@H) as a novel antimicrobial delivery system. Physicochemical techniques were used to successfully produce and characterize UNB@H nanoparticles, confirming their uniform size, excellent encapsulation efficiency, and structural integrity. pH-responsive drug release was 69.47% after 72 h, observed, with a sustained release under acidic conditions. The findings showed that UNB and UNB@H have extremely strong antibacterial activity. The findings of anti-biofilm activity tests showed that UNB@H significantly inhibited biofilms and downregulated the expression of efflux pump genes (MexA, MexB, norA, norB) and biofilm-related genes (icaA, icaB, ndvB, pelA) in all strains. The toxicity results indicated that the UNB@H exhibited 97.55 % cytotoxicity on HFF cells at a concentration of 50 μg/ml and 3.9% hemolysis, demonstrating excellent hemocompatibility. Additionally, H&E analysis confirmed in vivo wound infection investigations that demonstrated efficient infection control and faster healing. These results highlight UNB@H's potential as a multipurpose platform to fight antimicrobial resistance (AMR) by focusing on resistance mechanisms, biofilm formation, and offering biocompatible treatments for MDR infections.