Thermal Stabilization of Biologics with Photoresponsive Hydrogels
dc.contributor.author
Sridhar, Balaji V.
dc.contributor.author
Janczy, John R.
dc.contributor.author
Hatlevik, Øyvind
dc.contributor.author
Wolfson, Gabriel
dc.contributor.author
Anseth, Kristi S.
dc.contributor.author
Tibbitt, Mark W.
dc.date.accessioned
2022-08-02T06:48:42Z
dc.date.available
2018-02-12T08:19:34Z
dc.date.available
2018-04-09T13:02:04Z
dc.date.available
2018-05-18T14:51:51Z
dc.date.available
2018-05-24T10:44:28Z
dc.date.available
2022-08-02T06:48:42Z
dc.date.issued
2018-03-12
dc.identifier.issn
1525-7797
dc.identifier.issn
1526-4602
dc.identifier.other
10.1021/acs.biomac.7b01507
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/239949
dc.identifier.doi
10.3929/ethz-b-000239949
dc.description.abstract
Modern medicine, biological research, and clinical diagnostics depend on the reliable supply and storage of complex biomolecules. However, biomolecules are inherently susceptible to thermal stress and the global distribution of value-added biologics, including vaccines, biotherapeutics, and Research Use Only (RUO) proteins, requires an integrated cold chain from point of manufacture to point of use. To mitigate reliance on the cold chain, formulations have been engineered to protect biologics from thermal stress, including materials-based strategies that impart thermal stability via direct encapsulation of the molecule. While direct encapsulation has demonstrated pronounced stabilization of proteins and complex biological fluids, no solution offers thermal stability while enabling facile and on-demand release from the encapsulating material, a critical feature for broad use. Here we show that direct encapsulation within synthetic, photoresponsive hydrogels protected biologics from thermal stress and afforded user-defined release at the point of use. The poly(ethylene glycol) (PEG)-based hydrogel was formed via a bioorthogonal, click reaction in the presence of biologics without impact on biologic activity. Cleavage of the installed photolabile moiety enabled subsequent dissolution of the network with light and release of the encapsulated biologic. Hydrogel encapsulation improved stability for encapsulated enzymes commonly used in molecular biology (β-galactosidase, alkaline phosphatase, and T4 DNA ligase) following thermal stress. β-galactosidase and alkaline phosphatase were stabilized for 4 weeks at temperatures up to 60 °C, and for 60 min at 85 °C for alkaline phosphatase. T4 DNA ligase, which loses activity rapidly at moderately elevated temperatures, was protected during thermal stress of 40 °C for 24 h and 60 °C for 30 min. These data demonstrate a general method to employ reversible polymer networks as robust excipients for thermal stability of complex biologics during storage and shipment that additionally enable on-demand release of active molecules at the point of use.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
American Chemical Society
en_US
dc.rights.uri
http://rightsstatements.org/page/InC-NC/1.0/
dc.title
Thermal Stabilization of Biologics with Photoresponsive Hydrogels
en_US
dc.type
Journal Article
dc.rights.license
In Copyright - Non-Commercial Use Permitted
dc.date.published
2018-02-02
ethz.journal.title
Biomacromolecules
ethz.journal.volume
19
en_US
ethz.journal.issue
3
en_US
ethz.pages.start
740
en_US
ethz.pages.end
747
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
Washington, DC
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02130 - Dep. Maschinenbau und Verfahrenstechnik / Dep. of Mechanical and Process Eng.::02668 - Inst. f. Energie- und Verfahrenstechnik / Inst. Energy and Process Engineering::09472 - Tibbitt, Mark / Tibbitt, Mark
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02130 - Dep. Maschinenbau und Verfahrenstechnik / Dep. of Mechanical and Process Eng.::02668 - Inst. f. Energie- und Verfahrenstechnik / Inst. Energy and Process Engineering::09472 - Tibbitt, Mark / Tibbitt, Mark
en_US
ethz.date.deposited
2018-02-12T08:19:36Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-04-09T13:02:07Z
ethz.rosetta.lastUpdated
2024-02-02T17:44:45Z
ethz.rosetta.versionExported
true
ethz.COinS
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