Soft nanoparticles as antimicrobial agents and carriers of microbiocides for enhanced inhibition activity

Abstract

Antibiotic resistance continues to pose significant health challenges. Considering severe limitations in the discovery and supply of new antibiotics, there is unmet need in designing alternative and more effective strategies in addressing this global issue. Polymeric nanoparticles with cationic shell surface offer a highly promising approach in coupling their inherent bactericidal action with sustained delivery of small lipophilic microbicides. We have utilized this platform in assembling multi-tasking soft core-shell nanoparticles from star polymers with the desired asymmetric arms composition. These stable nanoparticles with low critical micelle concentration are imparted intrinsic antimicrobial potency due to high positive charge density in the corona, as well as loading of active biocidal agents (such as curcumin and terbinafine) for potential dual and coadjuvant inhibition. This strategic combination allows for both immediate (direct contact) and extended (drug delivery) antibacterial activity for better therapeutic efficacy. Micellar nanoparticles with and without therapeutic cargo were highly efficient against both Escherichia coli (E. coli)and Bacillus subtilis (B. subtilis), representativeGram-positive and Gram-negative bacteria, respectively. Interestingly, we observed bacteria- and concentration-dependent effects, in which higher concentration of charged-nanoparticles were more effective against E. coli, whereas B. subtilis were inhibited only at lower concentration. This work highlights a valuable platform to achieve combination therapy through nanoparticles with charged coronas and delivery of potent therapeutics to overcome antimicrobial resistance.