Controlling the Release of Small, Bioactive Proteins via Dual Mechanisms with Therapeutic Potential.

Autor:	Kharkar PM; Department of Materials Science and Engineering, University of Delaware, 201 DuPont Hall, Newark, DE, 19716, USA., Scott RA; Department of Materials Science and Engineering, University of Delaware, 201 DuPont Hall, Newark, DE, 19716, USA.; Nemours-Alfred I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE, 19803, USA., Olney LP; Department of Dermatology, School of Medicine, UC-Davis Medical Center, 2315 Stockton Blvd, Sacramento, CA, 95817, USA., LeValley PJ; Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, DE, 19716, USA., Maverakis E; Department of Dermatology, School of Medicine, UC-Davis Medical Center, 2315 Stockton Blvd, Sacramento, CA, 95817, USA., Kiick KL; Department of Materials Science and Engineering, University of Delaware, 201 DuPont Hall, Newark, DE, 19716, USA.; Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way, Newark, DE, 19711, USA., Kloxin AM; Department of Materials Science and Engineering, University of Delaware, 201 DuPont Hall, Newark, DE, 19716, USA.; Department of Chemical and Biomolecular Engineering, University of Delaware, 150 Academy Street, Newark, DE, 19716, USA.
Jazyk:	angličtina
Zdroj:	Advanced healthcare materials [Adv Healthc Mater] 2017 Dec; Vol. 6 (24). Date of Electronic Publication: 2017 Oct 12.
DOI:	10.1002/adhm.201700713
Abstrakt:	Injectable delivery systems that respond to biologically relevant stimuli present an attractive strategy for tailorable drug release. Here, the design and synthesis of unique polymers are reported for the creation of hydrogels that are formed in situ and degrade in response to clinically relevant endogenous and exogenous stimuli, specifically reducing microenvironments and externally applied light. Hydrogels are formed with polyethylene glycol and heparin-based polymers using a Michael-type addition reaction. The resulting hydrogels are investigated for the local controlled release of low molecular weight proteins (e.g., growth factors and cytokines), which are of interest for regulating various cellular functions and fates in vivo yet remain difficult to deliver. Incorporation of reduction-sensitive linkages and light-degradable linkages affords significant changes in the release profiles of fibroblast growth factor-2 (FGF-2) in the presence of the reducing agent glutathione or light, respectively. The bioactivity of the released FGF-2 is comparable to pristine FGF-2, indicating the ability of these hydrogels to retain the bioactivity of cargo molecules during encapsulation and release. Further, in vivo studies demonstrate degradation-mediated release of FGF-2. Overall, our studies demonstrate the potential of these unique stimuli-responsive chemistries for controlling the local release of low molecular weight proteins in response to clinically relevant stimuli. (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze:	MEDLINE
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