Just add water: hydratable, morphologically diverse nanocarrier powders for targeted delivery

Two major obstacles that limit the widespread usage of polymeric nanocarriers include the complexity of formulation methods and their stability during storage. To address both of these issues, here we present morphologically complex nanocarriers in a hydratable powder form, which bypasses the need for expensive, harsh, and/or time-consuming nanocarrier fabrication techniques. The powders are composed of carbohydrates and self-assembling polymer amphiphiles having a low glass transition temperature. Hydration requires less than one minute and only involves the addition of aqueous media (water or saline) to rapidly obtain self-assembled micelles, worm-like micelles (i.e. filomicelles), or polymersomes from poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-b-PPS) polymers. The formulated powders are highly stable, achieving hydration into monodisperse nanocarriers following >6 months of storage. Diverse drug cargoes were efficiently encapsulated during hydration, including hydrophobic small molecules for micellar morphologies, as well as individual and concurrent loading of both hydrophobic and hydrophilic molecules for vesicular morphologies. Hydrated polymersomes are shown to load hydrophilic biological macromolecules, and encapsulated enzymes retain bioactivity. Furthermore, we demonstrate that inclusion of lipid-anchored ligands in powder form permits the surface-display of targeting ligands and enhances target cell uptake, thereby extending this technology to targeted drug delivery applications. Our powder-based formulation strategy was extendable to commercially available polymer amphiphiles, including PEG-b-polystyrene and PEG-b-polycaprolactone. The formulated nanotechnologies described herein are highly modular, require minimal preparation, and remain stable in ambient long-term storage (bypassing cold chain requirements), which will enable their use in medicine (human and veterinary), research, and commercial applications from cosmetics to agriculture.