(670g) Evaluation of Poly(curcumin) Microparticle Degradation and Activity in the Presence of Free Radical Generating Systems

Under a variety of pathophysiological conditions (e.g., radiation injury, inflammation, acute lung injury), cells are no longer able to maintain a balance between antioxidants and exogenous or endogenous radical generation, resulting in free radicals overproduction and oxidative stress.

Curcumin, a potent antioxidant, has three potential scavenging sites, but due to its hydrophobicity, poor solubility and bioavailability, it has possessed a low therapeutic effect in vivo. Free antioxidant drug delivery systems can also pose strain to the environment that can lead to pro-oxidant effects rather than the latter. To overcome these limitations, our group has previously synthesized a covalently crosslinked poly(curcumin beta amino), poly(curcumin), film, where the hydrolytically degradable backbone of the polymer network increases curcuminâ??s bioavailability, utilizing a controlled release mechanism, which gives great potential to show positive efficacy on oxidative stress treatment and cellular protection. Poly(curcumin) films can be cryomilled into microparticles to employ versatility in size and for localized delivery of interest. An advantage of the poly(curcumin) network is its comonomer system composed of a hydrophilic (polyethylene glycol (400) diacrylate) and hydrophobic (curcumin multiacrylate (CMA)) component. The ratios of these components can be varied to modify the rate of drug release. The design of microparticle blends can provide unique regulation to future dosage and treatments to specific oxidative environments (e.g. different stages of oral mucositis) to maintain a constant therapeutic release of curcumin. The use of kinetic and predictive modeling can be used to model poly(curcumin) microparticles as a two compartment system to verify the contributing factors to microparticle degradation as well as the consumption or scavenging rates of the released curcumin. We hypothesize that curcumin release from microparticles of different compositions that are introduced to reactive oxygen species to the microparticle system will respond and consume differently based on different degradation rates. and accelerate the hydrolytic cleavage of the weak ester bonds, further accelerating the release and consumption of curcuminâ??s antioxidant activity due to its scavenging capabilities. Predictive models can allow for us to evaluate and understand our complex polymer network mechanistically and better understand the contribution of volume, hydrolysis, and drug affinity in our system.