Currently employed antibiotic treatments are losing their activity due to resistant bacterial strains, and the development of clinical alternatives is of primary importance. Prevalent research underscores efforts to engineer highly sophisticated nano-vesicles that are functionalized to combat antibiotic-resistant bacterial infections, especially those caused by methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), and that aid in wound healing or immunomodulation. This is especially relevant for patients who are susceptible to MRSA infections post-operatively. The purpose of this research is to (1) propose an alternative to antibiotics to which bacteria are non-resistant, (2) to describe the design of a suitable drug delivery vehicle, and (3) to contribute to a general knowledge about the mechanisms involved in the inhibition of bacterial growth through the use of antimicrobial peptides (AMPs) and metallic nanoparticles. Here, formulations were incorporated into polymeric, biocompatible vesicles called polymersomes that self-assemble via hydrophobicity interactions of admixed aqueous and organic substances. Nano-polymersomes were synthesized using a high molecular weight amphiphilic block copolymer and were conjugated to include antimicrobial peptides (AMPs) along the peripheral hydrophilic region and silver (Ag) nanoparticles inside their hydrophobic corona. <i>In vitro</i> testing on bacterial and human cell lines indicated that finely tuned treatment concentrations of AMP and Ag nanoparticles in polymersomes synergistically inhibited the growth of MRSA without posing significant side effects, as compared with other potent treatment strategies. In particular, a ratio of silver-to-AMP of about 1:1.9, corresponding to approximately 0.1 mg/ml of silver nanoparticles and 40 μM of the peptide, yielded complete MRSA inhibition over a 23-hour time frame. The silver nanoparticles generate bacterial cell wall indentations that prompt the influx of AMPs and the outflow of vital proteins or nutrients. This bacteriostatic activity, coupled with nominal cytotoxicity towards native human dermal fibroblast cells, extends the potential for AMP/Ag nanoparticle polymersome therapies to replace antibiotics clinically. This study will facilitate contemporary research that is feasible, important, and highly relevant, and possesses the potential to advance knowledge in several fields, including drug delivery, nanotechnology, and artificial immunity.

Peptide-enriched nanoparticle carriers for the growth inhibition of antibiotic-resistant bacteria

256th National Meeting (2018)

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