Injectable in situ dual-crosslinking hyaluronic acid and sodium alginate based hydrogels for drug release

A series of injectable in situ dual-crosslinking hydrogels (HA/ALG) based on oxidized sodium alginate (oxi-ALG) and hyaluronic acid modified with thiol and hydrazide (HA-SH/CDH) were prepared via hydrazone bonds and disulfide bonds. The chemical structures, morphologies, rheological properties, gelling time, swelling ratio, degradation rate and drug release behavior of hydrogels were investigated. HA/ALG hydrogels exhibited tunable gelling time, rheological properties, swelling ratio and degradation rate with varying precursor concentrations. The gelling time of HA/ALG hydrogels ranged from 157 s to 955 s, the values of yield stress of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were 1724, 4349 and 5306 Pa, and the degradation percentage of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were about 64%, 51% and 42% after incubating 35 days, respectively. Bovine serum albumin (BSA) was used as a model drug to investigate the drug controlled release properties, and the in vitro cumulative release percentage of BSA from HA2/ALG2, HA3/ALG3 and HA4/ALG4 drug-loaded hydrogels were about 79%, 72% and 69% after 20 days. The series of injectable in situ dual-crosslinking HA/ALG hydrogels could be an attractive candidate for drug delivery system, tissue engineering and regenerative medicine.

Injectable in situ dual-crosslinking hydrogels (HA/ALG) were prepared from thiol- and hydrazide-bifunctionalized hyaluronic acid (HA-SH/CDH) and oxidized alginates (oxi-ALG). Hydrogels exhibited tunable gelling time, appropriate rheology properties, high swelling ratio, low degradation percentage and sustainable controlled release properties, signifying that they could be potentially used in the fields of drug controlled release, cell encapsulation, tissue engineering and regenerative medicine.