Click-cross-linked, doxorubicin-loaded hydrogels based on poly(styrene-alt-maleic anhydride)

A new type of hydrogels based on poly(styrene-alt-maleic anhydride) (PSMA) was prepared via Diels-Alder click chemistry. The formulations consisting of tetrazine-functionalized PSMA as a multi-clickable polymer and norbornene-terminated poly(ethylene glycol) (PEG) as a polymeric cross-linker were used as precursors to give ultrafast hydrogels with controlled structures. The hydrogels formed within several minutes under a physiological condition without any catalyst, and their storage modulus (G') values were in the range 0.3-1.7 kPa suitable for bio-applications. The pore structure and the release profile of doxorubicin hydrochloride (DOX-HCl) of the hydrogels could be manipulated by the molecular weight of PEG. The precursors exhibited practically no depressing effect of the normal HEK293 growth, while the DOX-HCl-loaded hydrogel presented significant anticancer activity towards HeLa cells. The results suggested this biocompatible hydrogel as a potential injectable drug depot for tumor sites.