Tunable porosity of covalently crosslinked alginate-based hydrogels and its significance in drug release behavior

Task-specific drug release is essential in the development of hydrogels as drug delivery systems. The aim of the study is to report the effect of porosity on alginate hydrogels, which may be controlled by the design of crosslinkers, on drug release behavior. Two alginate-based hydrogels were prepared: alginate-norbornene (Alg-Nb) crosslinked by disulfide-tetrazine (S-Tz; hydrogel A) and alginate-furfuryl amine (Alg-FA) crosslinked by disulfide-maleimide (S-Ma; hydrogel B). Results showed the porosity of hydrogel A was controllable by adjusting the amount of S-Tz. Gel formation was facilitated by a "click" reaction between Alg-Nb and S-Tz, producing nitrogen gas, which, in turn, acted as an in-situ pore generator. Hydrogel B showed a non-porous morphology, as gelation was processed via addition reaction between Alg-FA and S-Ma, which produced no by-product. The study showed that crosslinker proportion and porosity were significant factors influencing drug release behavior of the alginate hydrogels. The presence of a porous structure increased the drug release while non-porous hydrogels led to a very slow release. In addition, the porous alginate hydrogels could sustainably release doxorubicin for 35 days.