Injectablein situcross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels for drug release

Abstract

A series of injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels (HA/CMC) was prepared via disulfide bonds by the oxidation of dissolved oxygen. The results showed that HA/CMC hydrogels exhibited tunable gelling time, appropriate rheology properties, high swelling ratio, good stability, and sustained drug release ability. The gelling time of HA/CMC hydrogels ranged from 1.4 to 7.0 min, and the values of the storage modulus, complex shear modulus, dynamic viscosity, and yield stress of HA3/CMC3 hydrogel were about 5869 Pa, 5870 Pa, 587 Pa·s, and 1969 Pa, respectively. The degradation percentage of HA1/CMC1, HA2/CMC2, and HA3/CMC3 hydrogels were about 60, 49, and 41% after incubating 42 days, and the in vitro cumulative release percentage of BSA from HA1/CMC1, HA2/CMC2, and HA3/CMC3 drug-loaded hydrogels were about 99, 91, and 82% after 30 days. The series of injectable in situ cross-linking HA/CMC hydrogels exhibited good comprehensive performance, signifying that these hydrogels could be potentially used in the fields of short- and medium-term controlled drug release, cell encapsulation, regenerative medicine, and tissue engineering.

Relationship between Structure and Rheology of Hydrogels for Various Applications

“…This crossover point is important because it indicates the kinetics of the gelation reaction. For instance, Deng et al used oscillatory time strain to evaluate the dependency of storage modulus (G’) and loss modulus (G”) of HA/CMC hydrogels over time and determined the gelling time at the crossover point of the G’ and G” curves [ 82 ]. However, Balakrishnan et al reported a limitation in this measurement because of the fast gelation of DDA-ChitHCl hydrogels—the gelation time could not be measured using oscillatory time sweep; nonetheless, the crossover point was still observed, and the storage modulus of the gel was higher than the loss modulus after gelling [ 83 ].…”

Glycosaminoglycan-Inspired Biomaterials for the Development of Bioactive Hydrogel Networks

“…Luo P et al [212] prepared composite hydrogels composed of oxidized hydroxyethyl cellulose covalently crosslinked with adipic acid dihydrazide modified HA. Thiolated derivatives of carboxymethyl cellulose and HA were used to produce injectable in situ crosslinkable hydrogels, by the formation of disulfide bonds, as a strategy for drug delivery systems [214].…”

Biopolymeric In Situ Hydrogels for Tissue Engineering and Bioimaging Applications

“…Bioactive injectable hydrogels of natural origin have been widely studied because of their excellent biodegradability and biocompatibility. Natural biomaterials frequently used in the fabrication of injectable hydrogels are cellulose [12], chitosan [13], collagen/gelatin [14,15], alginate [16], and hyaluronic acid [17].…”

“…These hydrogels can be loaded with bioactive drugs or nanoparticles in aqueous phase and be remodeled into the specified shape upon in vivo administration [17]. To enhance the physical and chemical properties of the injectable hydrogel, Deng et al [12] prepared cellulose-based hydrogels that were in situ cross-linked with hyaluronic acid and carboxymethyl cellulose via a disulfide bond formed by the oxidation of dissolved oxygen. The resulting injectable hydrogel showed a tunable gelation time, appropriate physical properties, a high swelling quantitative relation, adaptability, and sustained drug release ability.…”

“…This compound demonstrated a high thermal stability, low toxicity and the possibility of reusability. To enhance the physical and chemical properties of the injectable hydrogel, Deng et al [12] have prepared cellulose-based hydrogel that was in situ crosslinked with hyaluronic acid and carboxymethyl cellulose by the oxidation of dissolved oxygen via disulfide bonds. The resulting injectable hydrogel showed a tunable gelation time, applicable physical properties, high swelling quantitative relation, adaptability, and sustained drug release property.…”