Abstract

The rapid rise and prevalence of bacterial genetic resistance to antibiotics is having a drastic impact on human health today. This study explored the development and optimization of a polymersome nanocarrier formed from a biodegradable diblock copolymer to overcome such antibiotic resistance. Here, the polymersomes (Ps) were designed with silver nanoparticles embedded in the particle's hydrophobic membrane bilayer, and an ampicillin solution encapsulated in the particle's aqueous core in order to provide a dual-mechanism, concentrated, and less cytotoxic localized treatment. These silver nanoparticle-embedded polymersomes (AgPs) were subsequently tested for bactericidal function against Escherichia coli transformed with a gene for ampicillin resistance (bla). Results showed for the first time that the AgPs killed the antibiotic-resistant bacteria, whereas free antibiotic, encapsulated antibiotic without the addition of the silver nanoparticles, and AgPs without the addition of ampicillin did not (Fig 1). Figure 1. The growth kinetics of ampicillin-resistant E. coli was measured over 24 hours in the presence of differing concentrations of (A) AgPs loaded with 160µg/mL amp and (B) control tests of: AgPs synthesized from PBS, Ps synthesized from 1mg/mL amp, 1mg/mL free amp, and no treatment (pure PBS). (C) Transmission electron micrographs reveal that the AgPs orient “silver nanoparticle first” in order to interact with the bacterial outer membrane (white arrows). In this manner, this study introduces a novel nanomaterial that can effectively treat problematic, antibiotic-resistant infections in an improved capacity which should be further examined for a wide range of medical applications.

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