INVESTIGATOR: Elizabeth Kiesewetter, Rhode Island College
MENTOR: Brenton DeBoef, University of Rhode Island

SCIENTIFIC THEME: Environmental Health Sciences

ABSTRACT: Multi-drug resistance represents a major hurdle in disease treatment. While some polymeric approaches aimed at overcoming multi-drug resistance have shown promise, they are largely based on synthetically costly procedures or materials that cannot be metabolized to benign products in vivo. Polymeric systems for drug delivery are designed to mitigate the shortcomings of small molecule therapeutics: poor solubility, off-target effects and (multi-) drug resistance. The goal of the proposed research is to develop new classes of highly functionalized polyesters and polycarbonates with hydrolysis and materials properties profiles that are complementary to established systems for drug delivery applications. The ideal polymeric drug delivery vehicle is one that 1) possesses a polymer backbone that can be depolymerized by physiological or externally introduced catalysts; 2) is adaptable to various targeting and delivery vectors; and 3) has the ability to incorporate a wide range of therapeutic functional groups. Our preliminary studies suggest that organocatalysts for ring-opening polymerization are ideally suited for the synthesis of a range of polymers and block copolymers and can tolerate a variety of biologically compatible functional groups. In particular, the ability to synthesize block copolymers allows access to polymeric assemblies such as micelles and drug delivery particles. Procedures for the synthesis of carbonate and coumalic acid derived polymers and block copolymers will be developed and their properties, including potential for micelle and drug delivery particle formation, will be examined.

HUMAN HEALTH RELEVANCE: Biocompatible polymers can be employed as cell-penetrating agents to overcome multidrug resistance and mitigate off target effects. The goal of the proposed research is to develop a new platform of functionalizable lactone and carbonate monomers and methods for their polymerization that will complement the degradability of existing polymer systems while enhancing the diversity of biocompatible, degradable and deliverable macromolecular structures available for disease treatment.