8:16 AM Abstract No. 187 - ■ Dr. Constantin Cope Medical Student Research Award Alginate microspheres with magnetically triggered gemcitabine release

Abstract

Purpose Alginate microspheres could serve as an ideal drug delivery platform for selective transcatheter administration of gemcitabine to pancreatic tumors. This study aimed to modify gemcitabine release with ultrasmall superparamagnetic iron oxide (USPIO) clusters. We tested the hypothesis that USPIOs will adsorb drug and slow drug release. Further, we hypothesized that drug release can be accelerated by magnetic induction heating. Lastly, we investigated the CT and MR imaging properties of these microspheres loaded with USPIOs and barium salts. Materials and Methods Alginate microspheres were synthesized by gelation of alginate, calcium salts, USPIOs, and hydroxypropyl cellulose using microfluidic channels. USPIOs were prepared by chemical reduction of iron (III) chloride. Gemcitabine was added by diffusion in drug solution. Drug release studies were performed in triplicate by dialyzing microspheres and quantifying drug release via absorption spectroscopy. Heat triggered drug release studies were performed with an Ambrell EasyHeat producing oscillating magnetic fields (1.85 kW, 200 kHz). Imaging of microspheres was performed with Bruker 7T MRI and Somatom Sensation Cardiac 64 CT. Results At physiological conditions, the presence of USPIOs in alginate microspheres slowed the rate of drug release by an average of 25% compared with drug release from microspheres without USPIOs. Magnetic induction heating accelerated drug release by an average of 18% compared with control. Microspheres were imaged with CT and MRI demonstrating image contrast well correlated with barium and USPIO content. Conclusion USPIOs can slow the rate of gemcitabine release and induction heating can trigger an acceleration of drug release from these USPIO containing alginate microspheres. These microspheres provide image contrast for visualization with both CT and MRI modalities. Future animal model studies will evaluate the efficacy of these microspheres for selective transcatheter delivery of gemcitabine to pancreatic tumors.