The rise of multidrug-resistant strains of bacteria represents a major global threat. Often, infections by aggressive, drug-resistant strains of bacteria require combinations of drugs as a form of broad-spectrum treatment. However, these combinations may result in off-target toxicity and/or be ineffective at combating the bacteria and corresponding biofilms. The Barnes group at Washington University in St. Louis has designed a next-generation nanoparticle drug delivery system consisting of block copolymers prepared through ring-opening metathesis polymerization (ROMP) that can be loaded with any desired drug combination in a matter of minutes, followed by rapid (&lt;10s) self-assembly into nanoparticles which may be used immediately as a type of non-toxic treatment. The block copolymer bears macrocyclic drug- and antimicrobial-binding sites along the polymer backbone, as well as poly(ethylene glycol) side chains that help solubilize the polynorbornene-based nanoparticle. Additionally, a targeting and cellular membrane permeating block has been added to destabilize gram-negative bacteria membranes and facilitate drug delivery to bacteria cells. This supramolecular polymer strategy bypasses the toxicity of standard drug combinations, while also not employing pro-drugs, which may not undergo complete release or conversion to the free drug form in vitro/in vivo, and therefore could possess a different mechanism of action. In my talk, I will discuss the synthesis and characterization of this next-generation drug delivery platform, the corresponding drug release kinetics and cytotoxicity, as well as demonstrations of in vitro efficacy and cellular interaction against different strains of MDR bacteria.

Self-assembled supramolecular polymers for enhanced combination antimicrobial therapeutic treatment of drug-resistant bacteria

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.