Instantaneous Degelling Thermoresponsive Hydrogel

Responsive polymeric hydrogels have found wide application in the clinic as injectable, biocompatible, and biodegradable materials capable of controlled release of therapeutics. In this article, we introduce a thermoresponsive polymer hydrogel bearing covalent disulfide bonds. The cold aqueous polym...

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Main Authors: Noam Y. Steinman, Abraham J. Domb
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Gels
Subjects:
Online Access:https://www.mdpi.com/2310-2861/7/4/169
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author Noam Y. Steinman
Abraham J. Domb
author_facet Noam Y. Steinman
Abraham J. Domb
author_sort Noam Y. Steinman
collection DOAJ
description Responsive polymeric hydrogels have found wide application in the clinic as injectable, biocompatible, and biodegradable materials capable of controlled release of therapeutics. In this article, we introduce a thermoresponsive polymer hydrogel bearing covalent disulfide bonds. The cold aqueous polymer solution forms a hydrogel upon heating to physiological temperatures and undergoes slow degradation by hydrolytic cleavage of ester bonds. The disulfide functionality allows for immediate reductive cleavage of the redox-sensitive bond embedded within the polymer structure, affording the option of instantaneous hydrogel collapse. Poly(ethylene glycol)-b-poly(lactic acid)-S-S-poly(lactic acid)-b-poly(ethylene glycol) (PEG-PLA-SS-PLA-PEG) copolymer was synthesized by grafting PEG to PLA-SS-PLA via urethane linkages. The aqueous solution of the resultant copolymer was a free-flowing solution at ambient temperatures and formed a hydrogel above 32 °C. The immediate collapsibility of the hydrogel was displayed via reaction with NaBH<sub>4</sub> as a relatively strong reducing agent, yet stability was displayed even in glutathione solution, in which the polymer degraded slowly by hydrolytic degradation. The polymeric hydrogel is capable of either long-term or immediate degradation and thus represents an attractive candidate as a biocompatible material for the controlled release of drugs.
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spelling doaj.art-fe680d37cfc94ad681fc50a2cbfc0a7e2023-11-23T08:27:26ZengMDPI AGGels2310-28612021-10-017416910.3390/gels7040169Instantaneous Degelling Thermoresponsive HydrogelNoam Y. Steinman0Abraham J. Domb1The Alex Grass Center for Drug Design and Synthesis and Center for Cannabis Research, Faculty of Medicine, Institute of Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelThe Alex Grass Center for Drug Design and Synthesis and Center for Cannabis Research, Faculty of Medicine, Institute of Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelResponsive polymeric hydrogels have found wide application in the clinic as injectable, biocompatible, and biodegradable materials capable of controlled release of therapeutics. In this article, we introduce a thermoresponsive polymer hydrogel bearing covalent disulfide bonds. The cold aqueous polymer solution forms a hydrogel upon heating to physiological temperatures and undergoes slow degradation by hydrolytic cleavage of ester bonds. The disulfide functionality allows for immediate reductive cleavage of the redox-sensitive bond embedded within the polymer structure, affording the option of instantaneous hydrogel collapse. Poly(ethylene glycol)-b-poly(lactic acid)-S-S-poly(lactic acid)-b-poly(ethylene glycol) (PEG-PLA-SS-PLA-PEG) copolymer was synthesized by grafting PEG to PLA-SS-PLA via urethane linkages. The aqueous solution of the resultant copolymer was a free-flowing solution at ambient temperatures and formed a hydrogel above 32 °C. The immediate collapsibility of the hydrogel was displayed via reaction with NaBH<sub>4</sub> as a relatively strong reducing agent, yet stability was displayed even in glutathione solution, in which the polymer degraded slowly by hydrolytic degradation. The polymeric hydrogel is capable of either long-term or immediate degradation and thus represents an attractive candidate as a biocompatible material for the controlled release of drugs.https://www.mdpi.com/2310-2861/7/4/169PEG-PLAthermoresponsive hydrogelredox-sensitive
spellingShingle Noam Y. Steinman
Abraham J. Domb
Instantaneous Degelling Thermoresponsive Hydrogel
Gels
PEG-PLA
thermoresponsive hydrogel
redox-sensitive
title Instantaneous Degelling Thermoresponsive Hydrogel
title_full Instantaneous Degelling Thermoresponsive Hydrogel
title_fullStr Instantaneous Degelling Thermoresponsive Hydrogel
title_full_unstemmed Instantaneous Degelling Thermoresponsive Hydrogel
title_short Instantaneous Degelling Thermoresponsive Hydrogel
title_sort instantaneous degelling thermoresponsive hydrogel
topic PEG-PLA
thermoresponsive hydrogel
redox-sensitive
url https://www.mdpi.com/2310-2861/7/4/169
work_keys_str_mv AT noamysteinman instantaneousdegellingthermoresponsivehydrogel
AT abrahamjdomb instantaneousdegellingthermoresponsivehydrogel