Redox-Responsive Delivery Systems for Antimicrobial Resistance (AMR) Management

Antimicrobial resistance (AMR) threatens the health security of all countries, tearing down the efficacy of infection prevention and treatment and adding pressure on health systems across the world. In this chapter, we will discuss the promising approach to addressing the AMR issue by means of the novel redox-responsive drug delivery systems. RDDS utilize the changed redox condition in the infection microenvironment, involving increased RROS and RGS, to realize targeted and regulated release of antibiotics. Different kinds of RDDS, including nanoparticles, polymeric micelles, dendrimers, and redox-activated prodrugs, are described in terms of their characteristics to disturb bacterial redox homeostasis, and to promote drug accumulation at infected sites and at the same time reduce systemic toxicity. Furthermore, the chapter addresses approaches including inhibiting efflux pumps, CRISPR-Cas gene editing, and combination usage with quorum sensing inhibitors to compromise biofilms while resuscitating antibiotic sensitivity. Strong antibacterial efficacy and biofilm eradication have been observed in preclinical models with these redox-triggered systems, justifying their translational potential. Despite obstacles concerning bacterial adaptation and delivery maintenance, RDDS are powerful instruments for the worldwide One Health effort to combat AMR and increase the longevity of currently available antibiotics.