Targeted Nano-Encapsulated Ceftriaxone: Ligand–Receptor Interactions and Strategies to Overcome Efflux Pump-Mediated Resistance

Abstract

The issue of antimicrobial resistance is a serious health problem on the international level, which makes traditional antibiotics like ceftriaxone less effective. The mechanisms that limit the accumulation of intracellular drugs and impair the therapeutic outcomes include efflux pumps, enzymatic degradation, and reduced membrane permeability. One of the promising solutions to these challenges involves nanotechnology-based drug delivery system, which entails encasing the antibiotics into nanoscale systems, which not only stabilizes the drug, but also prevents degradation of the drug, but also allows the controlled and targeted release. Nano-encapsulation enhances conditions of ligand-receptor of ceftriaxone and bacterial targets, elevating local drug concentration, improving binding of penicillin-binding proteins, and improving residence time in the vicinity of bacterial membrane. Nanocarriers also resolve the resistance due to efflux by circumventing the traditional recognition pathways, sustained release of drugs, and co-delivery of ceftriaxone and efflux pump inhibitors. All these measures further compound the intracellular accumulation of the antibiotics, which guarantees constant exposure and overloading of the bacterial defences. Surface plasmon resonance, isothermal titration calorimetry, and fluorescence spectroscopy are experimental biophysical methods that can offer important information regarding the binding dynamics and efficacy of nano-encapsulated antibiotics, whereas molecular docking and molecular dynamics simulations are the two computational methods that present vital information on the binding dynamics and efficacy of nano-encapsulated antibiotics. The quality and performance of formulations and drug release are guaranteed by the dynamic light scattering, transmission electron microscopy and drug release analysis characterization of nanoparticles.

Keywords:  Nanoparticles, Antibiotic resistance, Efflux Pump.