Supramolecular Phenylalanine-Derived Hydrogels for the Sustained Release of Functional Proteins.

Content Provider	Europe PMC
Author	Jagrosse, MelissaL. Agredo, Pamela Abraham, Brittany L. Toriki, Ethan S. Nilsson, Bradley L.
Copyright Year	2023
Abstract	Protein-based therapeutics have emerged as next-generationpharmaceuticalagents for oncology, bone regeneration, autoimmune disorders, viralinfections, and other diseases. The clinical application of proteintherapeutics has been impeded by pharmacokinetic and pharmacodynamicchallenges including off-target toxicity, rapid clearance, and drugstability. Strategies for the localized and sustained delivery ofprotein therapeutics have shown promise in addressing these challenges.Hydrogels are critical materials that enable these delivery strategies.Supramolecular hydrogels composed of self-assembled materials havedemonstrated biocompatibility advantages over polymer hydrogels, withpeptide and protein-based gels showing strong potential. However,cost is a significant drawback of peptide-based supramolecular hydrogels.Supramolecular hydrogels composed of inexpensive low-molecular-weight(LMW) gelators, including modified amino acid derivatives, have beenreported as viable alternatives to peptide-based materials. Herein,we report the encapsulation and release of proteins from supramolecularhydrogels composed of perfluorinated fluorenylmethyloxcarbonyl-modifiedphenylalanine (Fmoc-F5-Phe-DAP). Specifically, we demonstraterelease of four model proteins (ribonuclease A (RNase A), trypsininhibitor (TI), bovine serum albumin (BSA), and human immunoglobulinG (IgG)) from these hydrogels. The emergent viscoelastic propertiesof these materials are characterized, and the functional and time-dependentrelease of proteins from the hydrogels is demonstrated. In addition,it is shown that the properties of the aqueous solution used for hydrogelformulation have a significant influence on the in vitro release profiles, as a function of the isoelectric point and molecularweight of the protein payloads. These studies collectively validatethat this class of supramolecular LMW hydrogel possesses the requisiteproperties for the sustained and localized release of protein therapeutics.
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Journal	ACS Biomaterials Science & Engineering [ACS Biomater Sci Eng]
Volume Number	9
DOI	10.1021/acsbiomaterials.2c01299
PubMed Central reference number	PMC9930093
Issue Number	2
PubMed reference number	36693219
e-ISSN	23739878
Language	English
Publisher	American Chemical Society
Publisher Date	2023-01-24
Access Restriction	Open
Rights License	Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). © 2023 The Authors. Published by American Chemical Society
Subject Keyword	hydrogel controlled release self-assembly drug delivery
Content Type	Text
Resource Type	Article
Subject	Biomaterials Biomedical Engineering