A novel polymer nanoparticle treatment for acute kidney injury
ORAL
Abstract
Acute kidney injury (AKI) is a common and often life-threatening surgery complication caused by an overproduction of reactive oxygen species (ROS) in the body. APP-103™ is a novel polymer-based therapeutic designed to treat and prevent AKI with an active ingredient, PVAX, that quenches ROS at the site of injury and releases an anti-inflammatory drug, vanillyl alcohol, as a product of this reaction. APP-103™ is formed by the emulsification-solvent evaporation method of nanoparticle formation. During this process, PVAX is dissolved into an organic solvent, dichloromethane (DCM), then added to a solution of polyvinyl alcohol (PVA) in water while undergoing high shear vortexing. As an emulsion forms, droplets of PVAX and DCM form and are stabilized by the PVA in the water phase. After the removal of excess DCM, centrifuge rinsing, and lypophilization, a powder of APP-103™ nanoparticles remains. Techniques including scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential measurements, and a hydrogen peroxide assay are used to characterize APP-103™. Ongoing work is aimed towards understanding the release kinetics of APP-103™ in contact with ROS and optimizing particle formulation for clinical use in humans.
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Publication: Lee, D., Bae, S., Hong, D. et al. H2O2-responsive molecularly engineered polymer nanoparticles as ischemia/reperfusion-targeted nanotherapeutic agents. Sci Rep 3, 2233 (2013).<br><br>Minami K, Bae S, Uehara H, et al. Targeting of intragraft reactive oxygen species by APP-103, a novel polymer product, mitigates ischemia/reperfusion injury and promotes the survival of renal transplants. Am J Transplant. 2020;20(6):1527-1537. <br><br>Soochan Bae et al. "Hydrogen Peroxide- Responsive Nanoparticle Reduces Myocardial Ischemia/Reperfusion Injury". In: Journal of the American Heart Association 5 (Nov. 2016), <br><br><br>
