Antibiotic-conjugated polyacrylate nanoparticles: New opportunities for development of anti-MRSA agents

This report describes the preparation of polyacrylate nanoparticles in which an N-thiolated β-lactam antibiotic is covalently conjugated onto the polymer framework. These nanoparticles are formed in water by emulsion polymerization of an acrylated antibiotic pre-dissolved in a liquid acrylate monomer (or mixture of co-monomers) in the presence of sodium dodecyl sulfate as a surfactant and potassium persulfate as a radical initiator. Dynamic light scattering analysis and electron microscopy images of these emulsions show that the nanoparticles are approximately 40 nm in diameter. The emulsions have potent in vitro antibacterial properties against methicillin-resistant Staphylococcus aureus and have improved bioactivity relative to the non-polymerized form of the antibiotic. A unique feature of this methodology is the ability to incorporate water-insoluble drugs directly into the nanoparticle framework without the need for post-synthetic modification. Additionally, the antibiotic properties of the nanoparticles can be modulated by changing the length or location of the acrylate linker on the drug monomer.

Antibacterially active polyacrylate nanoparticles in the range of 30–50 nm have been synthesized in water by emulsion polymerization of an N-thiolated β-lactam acrylate pre-dissolved in a mixture of butyl acrylate and styrene (7:3). The resulting emulsions display potent in vitro activity against MRSA.Figure optionsDownload as PowerPoint slide