A Platform Approach to Protein Encapsulates with Controllable Surface Chemistry

The encapsulation of proteins into core-shell structures is a widely utilised strategy for controlling protein stability, delivery and release. Despite the recognised utility of these microstructures, however, core-shell fabrication routes are often too costly or poorly scalable to allow for industrial translation. Furthermore, many scalable routes rely upon emulsion-techniques implicating denaturing or environmentally harmful organic solvents. Herein, we investigate core-shell protein encapsulation through single-feed, aqueous spray drying: a cheap, industrially ubiquitous particle-formation technology in the absence of organic solvents. We show that an excipient’s preference for the surface of the spray dried particle is well-predicted by its hydrodynamic diameter (D [Formula: see text]) under relevant feed buffer conditions (pH and ionic strength) and that the predictive power of D [Formula: see text] is improved when measured at the spray dryer outlet temperature compared to room temperature ([Formula: see text] = 0.64 vs. 0.59). Lastly, we leverage these findings to propose an adaptable design framework for fabricating core-shell protein encapsulates by single-feed aqueous spray drying.