2022 Annual Meeting

Drug Transport in Charged Polymers for Chemotherapy Drug Capture to Reduce Toxic Side Effects

Cancer remains the second most prevalent cause of death in the United States with chemotherapy serving as one of the most common methods of treatment. Doxorubicin, a common chemotherapy drug for treating cancers of the blood, breast, liver, stomach among others, is dosage limited due to its severe cardiac toxicity. As much as 50-80% of the drug does not enter the target site leading to excess drug spreading throughout the body and inducing severe side effects. We demonstrate here the ability for excess doxorubicin capture using functionalized hydrogels to reduce toxic side effects. This study focuses on the drug transport within a copolymer consisting of the ionomer 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), which provides the sulfonate groups (R-SO3H) and the cross-linker poly (ethylene glycol) diacrylate (PEGDA). The main goal of this study is to determine the mechanism for doxorubicin sorption as predominantly absorption/adsorption or a combination of both. Doxorubicin capture experiments were conducted in several different concentrations to determine the membranes’ drug capture ability. The degree of polymerization was fixed for our hydrogels and multiple membrane types were constructed with various surface area to volume ratios with the amount of charged groups identical. Plots were constructed with the experimental data analyzing the amount of drug captured by the membrane versus the remaining, unbound drug concentration at equilibrium. This data was then used to generate a Langmuir adsorption model which provides the membranes’ maximum doxorubicin capacities and affinities to the drug. The total capacity of the membranes remaining the same despite the different surface area to volume ratios signifies that the mechanism is primarily absorption, as the main contributing factor would only be the amount of charged groups (identical). Conversely, the difference in doxorubicin capacity of the membranes would indicate that the surface area to volume ratio is the governing factor and not the amount of charged groups making adsorption the primary mechanism. Currently, to the best of our knowledge, minimal to no data exists on drug transport within charged polymers for drug capture making this study essential for gaining a better quantitative understanding about the mechanism(s) of drug transport in hopes of designing more effective, implantable drug capture devices for use within patients. Future work includes conducting drug capture experiments with competing ions commonly found in human blood and utilizing a flowing, pressurized system to more accurately model the human circulatory system.