Glycosylated nanoparticles as efficient antimicrobial delivery agents

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Eissa, Ahmed M. ; Abdulkarim, Ali ; Sharples, Gary J. ; Cameron, Neil R. (2016)

Synthetic polymer nanoparticles that can be tailored through multivalent ligand display on the surface, while at the same time allowing encapsulation of desired bioactive molecules, are especially useful in providing a versatile and robust platform in the design of specific delivery vehicles for various purposes. Glycosylated nanoparticles (glyco-NPs) of a poly(n-butyl acrylate) (pBA) core and poly(N-2-(β-d-glucosyloxy)ethyl acrylamide) (p(NβGlcEAM)) or poly(N-2-(β-D-galactosyloxy)ethyl acrylamide) (p(NβGalEAM)) corona were prepared via nanoprecipitation in aqueous solutions of preformed amphiphilic glycopolymers. Well-defined block copolymers of (poly(pentafluorophenyl acrylate) (pPFPA) and pBA were first prepared by RAFT polymerization followed by postpolymerization functionalization with aminoethyl glycosides to yield p(NβGlcEAM-b-BA) and p(NβGalEAM-b-BA), which were then used to form glyco-NPs (glucosylated and galactosylated NPs, Glc-NPs and Gal-NPs, respectively). The glyco-NPs were characterized by dynamic light scattering (DLS) and TEM. Encapsulation and release of ampicillin, leading to nanoparticles that we have termed “glyconanobiotics”, were studied. The ampicillin-loaded glyco-NPs were found to induce aggregation of Staphylococcus aureus and Escherichia coli and resulted in antibacterial activity approaching that of ampicillin itself. This glyconanobiotics strategy represents a potential new approach for the delivery of antibiotics close to the surface of bacteria by promoting bacterial aggregation. Defined release in the proximity of the bacterial envelope may thus enhance antibacterial efficiency and potentially reduce the quantities of agent required for potency.\ud \ud
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