(31b) Modeling the Oxidative Consumption of Curcumin from Controlled Release Poly(beta amino ester) Microparticles in the Presence of a Free Radical Generating System

The balance between the basal level concentrations of both reactive oxygen species and antioxidants is an essential component to the regulation of a physiologically healthy cellular environment. Under a variety of pathophysiological conditions (e.g., radiation injury, inflammation, acute lung injury), cells are no longer able to maintain a balance between antioxidant and radical formation, which results in free radical overproduction and oxidative stress. Curcumin, a potent antioxidant, derived from the Indian spice, turmeric, has been a promising candidate for the control of inflammation and serves as a free radical scavenger. However, up to now, no double-blinded, placebo controlled clinical trial of curcumin has shown a positive benefit. The proper design of a controlled release system can enhance curcumin’s bioavailability and eliminate failures seen in the delivery of curcumin thus far. The incorporation of curcumin into the backbone of a hydrolytically degradable cross-linked hydrogel that utilizes poly(beta amino ester) chemistry can provide a tunable protective network to release antioxidants at a controlled rate. The kinetics of this controlled release delivery system in the presence of oxidative environments has not yet been studied and can be used to investigate the consumption rates of active curcumin and degradation products to provide efficient therapy as a therapeutic.

Based on experimental data obtained, we developed a model that describes the concentration of curcumin as a free molecule in the presence of a general free radical generator, 2,2’-azobis(2-amidinopropane) dihydrochloride, over time. The set of mathematical expressions were solved simultaneously while the unknown consumption rate parameter of curcumin was minimized over the experimental data by sum of squared errors. These parameters were then used to find consumption rate parameters of additional degradation products found within the solution from a fully degraded microparticle system. From these results, we can quantify theoretical levels of free radicals present in an environment depending on the rate of release of curcumin provided. Modeling our drug delivery system will allow for improved translation and success overall in the delivery of curcumin as a therapeutic agent.