Injectable and biocompatible alginate-derived porous hydrogels cross-linked by IEDDA click chemistry for reduction-responsive drug release application

In this work, novel injectable and reduction-responsive hydrogels were successfully prepared via inverse electron demand Diels-Alder reaction between alginate-norbornene and a water-soluble PEG based disulfide cross-linker. The reduction-responsive cross-linker was designed to contain a PEG chain within two disulfide linkages, and two terminal tetrazine groups. The resulting hydrogels possessed high swelling ratios, porous morphology, excellent drug loading efficiency (similar to 92%), and suitable mechanical properties. The drug release experiments demonstrated that the hydrogels released more than 90% of the encapsulated doxorubicin (DOX) in the presence of 10 mM glutathione while a minimal DOX release (<25%) was measured in physiological buffer (PBS, pH = 7.4) after 11 d. The cross-linker and hydrogels did not exhibit any apparent cytotoxicity to fibroblast cells. In contrast, DOX-loaded hydrogels induced anti-tumor activity against cancer cells. The injectable and reduction responsive hydrogels hold great potential as a biomaterial for stimuli responsive drug delivery applications.

Automated summary

Novel injectable and reduction-responsive hydrogels were successfully prepared in this study. The hydrogels exhibited high swelling ratios, porous morphology, excellent drug loading efficiency, and suitable mechanical properties. Drug release experiments showed that the hydrogels released the encapsulated drug in the presence of glutathione and exhibited anti-tumor activity against cancer cells. These hydrogels have great potential as a biomaterial for stimuli responsive drug delivery applications.