Nanoparticles for delivery of pifithrins to combat cell death due to chemotherapy and radiation

Abstract

This work describes the first stage of our research efforts to develop targetable nanoparticles to deliver agents to help healthy bone marrow cells survive radiation and chemotherapy. Administering pifithrin, a small molecule inhibitor of the protein p53, could prevent p53 initiated cell death. The p53 protein imparts sensitivity to normal tissue subjected to genotoxic stress such as radiation therapy or chemotherapy. We describe the conversion of pifithrin-α to pifithrin-β in buffer and serum and even while frozen and the implications in developing successful formulations. Encapsulation of pifithrin-β in biodegradable nanoparticles of poly(lactic-co-glycolic) acid showed encapsulation of up to 13 wt% pifithrin and release in vitro of at least 28 days. Particle sizes ranged from 240 to 3250 nm, depending on the preparation methods used including variation of organic solvent type and amount.