Self-Delivery Nanomedicine for Targeted Antibacterial and Anti-inflammatory Therapy of Subcutaneous Skin Infection

Abstract

Antibiotic treatment for bacterial infections is often hindered by low bioavailability and significant side effects. Meanwhile, the excessive production of reactive oxygen species (ROS) in infectious sites exacerbates tissue damage and delays the wound healing progress. Nanomedicine offers a promising solution through enhancing antibiotic delivery and scavenging harmful ROS. Herein, we prepare a carrier-free antibacterial nanomedicine (termed as NEP) based on the self-assembly of nitrofural (NIT), epigallocatechin-3-gallate (EGCG), and phenylboric acid (PBA) via noncovalent bonds and formation of borate ester bonds between EGCG and PBA. NEP improves the biosafety and bioavailability of NIT and EGCG, while PBA enhances bacterial targeting. Moreover, NEP ensures the release of NIT to kill bacteria and EGCG to mitigate oxidative stress at the infection sites. Both in vitro and in vivo assays demonstrate the enhanced sterilization and anti-inflammatory effect of NEP. Therefore, the integration of NIT, EGCG, and PBA in a self-delivery system synergistically improves the antibacterial efficacy of NIT, anti-inflammatory capacity of EGCG, and bioavailability of both drugs, which offers a safer and more efficient treatment for subcutaneous skin infections.