(760d) Electrospinning Polymer Nanomedicines Extends Shelf-Life and Size Stability

Polymeric nanoparticle drug formulations can increase drug bioavailability and lower toxicity when compared to the free drug. However, nanoparticles require drying to improve long-term size stability and shelf-life for clinical use e.g. chemotherapy. To maintain threptic efficacy, drying techniques must avoid irreversible aggregation, redispersion should not require high-energy mixing e.g. sonication, and the redispersed solution must have appropriate osmolarity for intravenous administration. Current drying techniques, freeze-drying and spray-drying, require high concentrations of cyroprotectants (sugars) to avoid irreversible aggregation but the resulting dispersions can be hypertonic. We propose to dry nanoparticles via electrospinning with water-soluble polymers to decrease the osmolality of the redispersed nanoparticles while maintaining nanoparticle size. In electrospinning, a dissolved polymer is extruded, as an electric field is applied, and the polymer jet is elongated into nanofibers that are collected in a nonwoven pattern. Flash Nanoprecipitation (FNP) a bottom-up, polymer directed self-assembly method, was used to create polymer nanoparticles because it is a rapid and scalable method for encapsulating drugs into nanoparticles with high drug loading and narrow size distribution. Polyvinyl alcohol (PVA) was used for electrospinning as proof-of-concept. The polymer nanoparticles were added to dissolved polymer solution and electrospun. The nanoparticles were redispersed in aqueous solution using hand-mixing, a low energy method. Nanoparticle to nanofiber diameter (NP:NF) ratio was found to influenced nanoparticle size stability. Higher NP:NF ratio improve size stability after redispersion up to no change in size. A liquid core (vitamin E) nanoparticle was shown to have a 2-fold lower change in particle size after drying compared to solid core (polystyrene) nanoparticle. We attribute the difference due to liquid particle deformation under the shear stresses of fiber formation. Nanoparticle loading of 3.2% mass of nanoparticles to mass of polymer was achieved with no change in nanoparticle size upon reconstitution. Additionally, nanoparticle size upon reconstitution was not altered by storage time of at least 5 months at room temperature.