Development of Nanoparticle-Based Drug Delivery Systems Against Multidrug-Resistant (MDR) Bacteria

Abstract

Nanoparticle-based drug delivery systems (NDDSs) have attracted considerable interest as a potential method to effectively treat multidrug-resistant (MDR) bacterial infections, which pose increasing risks to the global community’s health. With the emergence of MDR bacteria, the antimicrobial resistance (AMR) phenomenon results in diminished efficacy of current traditional antibiotics and increases in morbidity, mortality, and cost of healthcare services. The accelerated global spread of resistance mechanisms such as, but not limited to, enzymatic degradation of the drug molecules, increased expression of efflux pumps, biofilm development/formation, and modification of the target site have created a pressing need for new therapeutic options. NPs give the potential unique opportunity to combat MDR bacterial infections due to their nanoscale size, high surface area, ability to be chemically modified to create uniquely tunable set of physical and chemical properties, and the ability to encapsulate a broad spectrum of antimicrobial agents. NPs can also provide enhanced stability through improved control over the interaction of the drug with the patient and/or environment. The variety of NDDS types, such as liposomes, well-defined polymeric NPs, solid lipid NPs, nanostructured lipid carriers, metallic NPs, dendrimers, and mesoporous silica NPs have been shown to possess significant antibacterial activity against clinically relevant MDR pathogens, including MRSA, carbapenem-resistant A. baumannii, PdR P. aeruginosa, K. pneumoniae, and E. coli. There are several mechanisms through which NPs can provide therapeutic benefits to combat antibiotic resistance (AMR), including disrupting bacterial cellular membranes, aiding in the penetration of antibiotics into microbial biofilms, inhibiting efflux pumps, producing reactive oxygen species (ROS), and achieving targeted intracellular delivery of the therapeutic. This review presents recent advances in the development and use of NDDS for the treatment of MDR bacterial infections, as well as their mechanisms of action, therapeutic applications, current challenges, and future directions. The combination of nanotechnology with personalized medicine, artificial intelligence (AI), and intelligent NDDS will likely facilitate the speedier development of the next generation of antimicrobial agents to address the public health threat of global AMR due to the emergence of MDR bacteria, and that innovative approaches to manage the ever-increasing problem of MDR bacteria are essential.