An injectable PEG hydrogel controlling neurotrophin-3 release by affinity peptides.
Affinity-controlled release
Injectable hydrogel
Michael addition
Neurotrophin-3
Phage display
Round window membrane
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
10 02 2021
10 02 2021
Historique:
received:
31
07
2020
revised:
21
12
2020
accepted:
22
12
2020
pubmed:
31
12
2020
medline:
8
7
2021
entrez:
30
12
2020
Statut:
ppublish
Résumé
Neurotrophin-3 growth factor can improve cochlear neuron survival, and localized delivery of this protein to the round window membrane in the middle ear may be able to reverse sensorineural hearing loss. Thus, the goal of this work was to develop an injectable hydrogel delivery system that can allow localized release of neurotrophin-3 in a controlled and sustained manner. We identified a PEG hydrogel formulation that uses thiol-vinyl sulfone Michael addition for crosslinking. This injectable formulation provides elastic hydrogels with higher mechanical rigidity, better bio-adhesion and longer residence time than Poloxamer hydrogels currently being investigated clinically for hearing loss. In vivo, PEG hydrogels induce local immune responses comparable to biocompatible Poloxamer hydrogels, yet they released payloads at a ~5-fold slower rate in the subcutaneous area. Based on this injectable hydrogel formulation, we designed an affinity-based protein release system by modifying PEG hydrogels with affinity peptides specific to neurotrophin-3 proteins. We verified the sustained release of neurotrophin-3 from peptide-conjugated PEG hydrogels resulting from the reversible interaction between peptides and proteins. The rate of affinity-controlled release depends on the polymer concentrations, the affinity of peptides and the peptide-to-protein ratios. Collectively, we developed an injectable hydrogel formulation for localized delivery of neurotrophin-3, which provides affinity-controlled release and longer delivery time compared to Poloxamer hydrogels.
Identifiants
pubmed: 33378693
pii: S0168-3659(20)30769-0
doi: 10.1016/j.jconrel.2020.12.045
pmc: PMC8783643
mid: NIHMS1658073
pii:
doi:
Substances chimiques
Biocompatible Materials
0
Hydrogels
0
Peptides
0
Proteins
0
Poloxamer
106392-12-5
Polyethylene Glycols
3WJQ0SDW1A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
575-586Subventions
Organisme : NIAID NIH HHS
ID : R01 AI148076
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC004820
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB005678
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS117103
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
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