P-glycoprotein (P-gp) is a membrane protein innately expressed at barrier sites in the body, including the blood-brain barrier, intestines, and many different cancers. P-gp binds small molecules, termed “substrates,” that present intracellularly and effluxes them to the cell exterior. These compounds include low molecular weight drugs, toxins, and metabolites, and their removal from tissues is typically protective. In cancer, P-gp recognizes a vast array of chemotherapeutic compounds as substrates, and its efflux activity results in prompt removal of these chemotherapeutics from cancer cells. This phenomenon imparts a cellular phenotype known as “multidrug resistance,” or MDR, and prevents effective therapeutic drug concentrations from being maintained within the cancer cells. This dissertation explores the chemical conjugation of quinidine, a P-gp inhibitor, to polymers as a way to permit P-gp inhibition while mitigating off-target cardiac effects associated with intravenous quinidine. First, quinidine is bound at its hydroxyl group to a single poly(ethylene glycol) chain, the resulting conjugate’s mechanism of action is verified, and its mitigated distribution into the myocardium is quantified. Next, a multivalent array of acrylic acid-quinidine copolymers are synthesized, chemically evaluated, and prepared for analysis of their biodistribution to P-gp bearing tissues in a rodent tumor xenograft model. This thesis highlights the capability of using the additions of polymers to quinidine to control its mechanism of action, mitigate its side effects, and tentatively influence biodistribution.