Dual-crosslinked Alginate/Carboxymethyl Chitosan Hydrogel Containing in situ Synthesized Calcium Phosphate Particles for Drug Delivery Application

Dual-crosslinked alginate/carboxymethyl chitosan (CMC) based hydrogels containing in situ synthesized calcium phosphate (CaP) particles were developed by combining two physical crosslinking, the ionic crosslinking of alginate with divalent cation (Ca2+), and the electrostatic interaction between cation of amino groups on CMC and anion of carboxyl groups on alginate. The calcium phosphate particles were in situ synthesized by using the excess Ca2+ of ionic crosslinking. The developed hydrogels were investigated the rheological properties, swelling behavior, degradation, and drug released performance in both water-soluble and insoluble drug models. The results showed that the viscoelasticity and swelling capacity of dual-crosslinked hydrogels were enhanced comparing the single-crosslinked alginate-based hydrogel. The in situ gelation of the developed hydrogel provided the injectable ability and drug-encapsulated capacity. Beside, calcium phosphate, including hydroxyapatite (HAp) was in situ synthesized during the gelation. Biocompatibility of this injectable hydrogel was studied by encapsulation behavior of human adipose-derived stem cells (ASCs). With these qualities, the developed hydrogel may have potential for medical providers such as hydrogel injections and drug providers.