Macromolecular prodrugs have the potential to increase the therapeutic window of small molecule drugs, but their limited synthetic modularity and scalability have hindered widespread clinical translation. We have developed an efficient, convergent synthesis of highly branched macromolecular prodrugs that enables the rapid incorporation of a wide range of therapeutic agents including small molecule and biologic drugs. The modularity of our approach allows for precise tuning of unmodified drug release mechanism and rate, which directly translates to improved therapeutic windows <i>in vivo</i>. In addition, this system is readily scalable, generating macromolecular prodrugs with identical characteristics from the 10 mg to the 1 kg scale. This talk will introduce our approach to macromolecular prodrug synthesis, and will discuss preclinical scaling, safety, and efficacy studies in the context of liver fibrosis and caner. Lastly, efforts to merge nitroxide-based magnetic resonance imaging with controlled release of therapeutics for image-guided drug delivery will be presented.

Highly branched polymers prepared via ring-opening metathesis polymerization of macromonomers: Syntheses and applications as prodrugs and biological imaging agents

2019 Spring National Meeting

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