Microgels with tunable affinity-controlled protein release desolvation of self-assembled peptide nanofibers

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2016-05, Vol.4 (18), p.354-364
• Main Authors: Fettis, Margaret M, Wei, Yaohua, Restuccia, Antonietta, Kurian, Justin J, Wallet, Shannon M, Hudalla, Gregory A
• Format: Article
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/c5tb02446c

With a growing number of bioactive protein drugs approved for clinical use each year, there is increasing need for vehicles for localized protein delivery to reduce administered doses, prevent off-target activity, and maintain protein bioactivity. Ideal protein delivery vehicles provide high encapsulation efficiency of bioactive drug, enable fine-tuning of protein release profiles, are biocompatible, and can be administered via minimally-invasive routes. Here we developed an approach to create micron-sized hydrated gels ( i.e. "microgels") for protein delivery that fulfill these requirements via desolvation of self-assembled β-sheet peptide nanofibers. Specifically, aqueous solutions of peptide nanofibers were diluted under stirring conditions in a "desolvating agent", such as ethanol, which is miscible with water but poorly solvates peptides. The desolvating agent induced nanofiber physical crosslinking into microgels that retained β-sheet secondary structure and were stable in aqueous solutions. Microgels did not activate dendritic cells in vitro , suggesting they are biocompatible. Peptide nanofibers and proteins having similar non-solvent immiscibility properties were co-desolvated to produce protein-loaded microgels with loading efficiencies of ∼85%. Encapsulated bioactive proteins rapidly diffused into bulk aqueous media, as expected for hydrated gels. Modifying peptide nanofibers with a protein-binding ligand provided tunable affinity-controlled protein release. Biocompatible microgels formed via desolvation of self-assembled peptide nanofibers are therefore likely to be broadly useful as vehicles for localized delivery of bioactive proteins, as well as other therapeutic molecules. We demonstrate an approach to fabricate microgels from self-assembled peptide nanofibers via desolvation. Proteins can be co-desolvated with nanofibers to create protein-loaded microgels. Modifying nanofibers with a protein-binding ligand provides tunable affinity-controlled protein release.