Encapsulation Strategy Matters: Pre- and Post-Loading of Macromolecules into Surface-Supported Microgels Formed via Vaterite Templates.

Calcium carbonate vaterite crystals have attracted increasing attention as sacrificial templates for forming polymer microgels. Vaterite's porous structure, biocompatibility, and eco-friendly synthesis make it ideal for biomedical applications. In this study, vaterite is grown on the surface, and surface-supported (ss)-microgels are formed by coating it with alternating layers of polyelectrolytes, sodium alginate (ALG), and poly-l-lysine (PLL), followed by core dissolution. Pre-loading (during vaterite synthesis) and post-loading (after microgel formation) of macromolecules are compared using dextran and its charged derivatives. Pre-loading proved to be more efficient, achieving up to 9% w/w encapsulation. Dextran adsorption follows the Langmuir model (ΔG = - 31.0 kJ/mol), while its derivatives follow the Freundlich model (1/n = 0.7-0.8), indicating intermolecular repulsion. Post-loading resulted in encapsulation levels below 1% w/w and exhibited pH-independent behavior. The microgels remained stable in acidic environments, but PLL degradation via trypsin enabled the sustained release of dextran. These findings clarify the mechanisms of macromolecular adsorption on ss-vaterite, highlight the importance of considering the loading strategy when designing microgels for specific applications, and support the use of ss-microgels for therapeutic delivery.