Rapid, Room Temperature Nanoparticle Drying and Low-Energy Reconstitution via Electrospinning

Abstract

Nanoparticle formulations offer advantages over free drugs; however, stability of the nanoparticle dispersions is a significant obstacle, and drying is often required for long-term size stability. The main limitation of current drying methods is particle aggregation upon reconstitution which can be overcome with sonication (impractical in a clinical setting) or large amounts of cryoprotectants (result in hypertonic dispersions). Therefore, new approaches to nanoparticle drying are necessary. We demonstrate conversion of nanoparticle dispersions to a dry, thermostable form via electrospinning. As a proof-of-concept, polyethylene glycol stabilized nanoparticles and polyvinyl alcohol were blended and electrospun into ∼300 nm fibers. Following electrospinning, nanoparticles were stored for at least 7 months and redispersed with low osmolarity to their original size without sonication. The nanoparticles redisperse to their original size when the fiber diameter and nanoparticle diameter are comparable (nanoparticle:nanofiber ratio ∼1). Nanoparticles with liquid cores and larger particles better maintained their size when compared to nanoparticles with solid cores and smaller particles, respectively. Storing the nanoparticles within nanofibers appears to prevent Ostwald ripening improving thermostability. Overall, this novel approach enables rapid, continuous drying of nanoparticles at room temperature to facilitate long-term nanoparticle storage. Improved nanoparticle drying techniques will enhance clinical translation of nanomedicines.

Keywords: drying; nanoparticles; nanotechnology; polymers; stabilization.