Hyaluronic acid based nanoparticles that mediate sustained thanatin release protect against NDM-1–resistant bacterial infections in a murine model

Abstract

Thanatin, a potent cationic antimicrobial peptide, has demonstrated remarkable efficacy against new NDM-1 producing bacteria. However, its clinical application is hampered by suboptimal stability in circulation and limited bioavailability in the human body. To overcome these challenges, a novel thanatin nanomedicine has been developed, which encapsulated thanatin in nanoparticles formed by electrostatic interactions between negatively charged HA and PLGA. The obtained ThaNPs demonstrated good stability, low cytotoxicity, and good metabolic ratio. ThaNPs significantly improve the stability of thanatin in the circulation, increasing its half-life in 50 % serum from 0.6 h to 3.2 h. Notably, the protective effect of ThaNPs against sepsis induced by NDM-1–producing Escherichia coli. was 10-fold higher than that of unencapsulated thanatin. These findings suggest that hyaluronic acid-based nanoparticles have the potentiality to overcome the clinical limitations associated with cationic antimicrobial peptides, thereby providing a novel and effective strategy for treating severe infections caused by antibiotic-resistant bacteria.