Multiphase Assembly of Small Molecule Microcrystalline Peptide Hydrogel Allows Immunomodulatory Combination Therapy for Long-Term Heart Transplant Survival.
hydrogels
immunotherapy
peptides
self-assembly
transplants
Journal
Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
04
05
2020
revised:
02
07
2020
pubmed:
20
8
2020
medline:
24
6
2021
entrez:
20
8
2020
Statut:
ppublish
Résumé
Combination therapies that target multiple pathways involved in immune rejection of transplants hold promise for patients in need of restorative surgery. Herein, a noninteracting multiphase molecular assembly approach is developed to crystallize tofacitinib, a potent JAK1/3 inhibitor, within a shear-thinning self-assembled fibrillar peptide hydrogel network. The resulting microcrystalline tofacitinib hydrogel (MTH) can be syringe-injected directly to the grafting site during surgery to locally deliver the small molecule. The rate of drug delivered from MTH is largely controlled by the dissolution of the encapsulated microcrystals. A single application of MTH, in combination with systemically delivered CTLA4-Ig, a co-stimulation inhibitor, affords significant graft survival in mice receiving heterotopic heart transplants. Locoregional studies indicate that the local delivery of tofacitinib at the graft site enabled by MTH is required for the observed enhanced graft survival.
Identifiants
pubmed: 32812339
doi: 10.1002/smll.202002791
pmc: PMC7686956
mid: NIHMS1642168
doi:
Substances chimiques
Hydrogels
0
Peptides
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2002791Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC011313
Pays : United States
Informations de copyright
© 2020 Wiley-VCH GmbH.
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