Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 11349-11359 |
| Number of pages | 11 |
| Journal | Nanoscale |
| Volume | 13 |
| Issue number | 26 |
| DOIs | |
| State | Published - Jul 14 2021 |
Funding
M.P.V. gratefully acknowledges support from the Ryan Fellowship, the International Institute for Nanotechnology at Northwestern University, and the Northwestern University Multidisciplinary Visual Sciences Training Program (T32 Fellowship funded by NEI Award 2T32EY025202-06). We acknowledge staff and instrumentation support from the Structural Biology Facility at Northwestern University, the Robert H Lurie Comprehensive Cancer Center of Northwestern University and NCI CCSG P30 CA060553. The Gatan K2 direct electron detector was purchased with funds provided by the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust. This work made use of the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. This work made use of the IMSERC at Northwestern University, which has received support from the NSF (CHE-1048773); Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205). This work was supported by the Northwestern University – Flow Cytometry Core Facility supported by Cancer Center Support Grant (NCI CA060553). SAXS experiments were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) that is located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, E.I. DuPont de Nemours & Co., and The Dow Chemical Company. This research was supported by the National Institutes of Health Director’s New Innovator Award (grant no. 1DP2HL132390-01), National Institute of Allergy and Infectious Diseases (grants no. 5R21AI137932 and 1R01AI145345), and the National Science Foundation CAREER Award no. 1453576.
ASJC Scopus subject areas
- General Materials Science
