Assistant Professor University of Tennessee Knoxville, Tennessee, United States
Introduction: Amygel is a novel injectable hydrogel designed for local chemotherapy delivery to solid tumors. We intend to optimize the encapsulation and loading of surrogate cations, determine the release kinetics of surrogate cations, and assess the encapsulation of α-emitting radionuclides within the hydrogel delivery system alone or as impregnated with radio-PLGA nanoparticles. It is anticipated that a high encapsulation of α-emitting radionuclides and high retention of decay daughters within the hydrogel delivery system will provide a viable route to advance the use of these radiotherapeutic anticancer agents in patient treatment.
Materials and
Methods: We have developed an aseptic microwave-assisted organic synthesis method to synthesize the Amygel starch hydrogel for optimized hydrogel biodegradation and drug release kinetics. Method development is straightforward, and we have deep experience in hydrogel synthesis. When we incorporate payloads into Amygel during polymer synthesis, we achieve 100% drug loading. To systematically construct Amygel network architecture formulations to test for optimized sustained-release and maximum tumor cytotoxicity, we will use rheology, Fourier Transform Infra-Red analysis, and Small Angle Neutron Scattering.
Results, Conclusions, and Discussions: Radionuclides and nanoparticles loaded with radionuclides were successfully incorporated into the hydrogel system and be released in their active form. These formulations were characterized using rheology, FTIR, Small Angle Neutron Scattering, and in vitro release studies. Patient derived tumor cells were cultured and treated with either dissolution media obtained from the in vitro dissolution studies, standard serial concentrations of chemotherapy agents in solution, or direct exposure to drug loaded Amygel. The activity of the chemotherapy agents were analyzed at 24 hr post-treatment, and the percentage of viable cells present in the culture at each time point was calculated using a CCK-8 kit with the absorbance read using a Multiskan Biochromatic Elisa plate reader.
