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 NaBH4 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.
Keywords: PEG-PLA; redox-sensitive; thermoresponsive hydrogel.