Issue 18, 2016

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

Abstract

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.

Graphical abstract: Microgels with tunable affinity-controlled protein release via desolvation of self-assembled peptide nanofibers

Supplementary files

Article information

Article type
Paper
Submitted
21 Du 2015
Accepted
08 Cʼhwe. 2016
First published
11 Cʼhwe. 2016

J. Mater. Chem. B, 2016,4, 3054-3064

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

M. M. Fettis, Y. Wei, A. Restuccia, J. J. Kurian, S. M. Wallet and G. A. Hudalla, J. Mater. Chem. B, 2016, 4, 3054 DOI: 10.1039/C5TB02446C

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