Redox- and pH-responsive alginate-based magnetic hydrogel: “Smart” drug delivery and protein corona studies

Abstract

A redox- and pH-responsive magnetic hydrogel was designed and developed based on alginate (Alg) through double crosslinking approach for sustained and targeted delivery of doxorubicin (Dox). For this objective, Fe3O4 nanoparticles (NPs) were synthesized by a chemical co-precipitation method, and then their surfaces were modified using an amine-end capped silane coupling agent. Alginate was oxidized using sodium periodate. Then, an alginate-based pH- and redox-responsive magnetic hydrogel with and without Dox loading was synthesized by adding amine-modified Fe3O4 NPs and cystamine (Cys) moiety through “Schiff-Base” condensation followed by double crosslinking with CaCl2. Drug loading and encapsulation efficiencies were quantified as 3.4 ± 0.27 and 83 ± 2.7%, respectively. Drug release study by dialysis method approved pH- and redox-dependent drug release behavior. Interactions between hydrogel and human serum albumin (HSA) was investigated using spectroscopy techniques, and it was found that the developed hydrogel can interact strongly with HSA. The thermodynamic parameters of the protein-hydrogel interaction were also calculated, and it was revealed that interaction process is spontaneous and endothermic. The anti-cancer activity of the developed magnetic DDS was assessed against MCF7 cells by MTT assay. It was found that free Dox had a stronger cytotoxic effect in the first 24 and 48 h in comparison with Dox-loaded DDS, while after 72 h, the DDS showed higher anti-cancer activity, possibly due to the controlled release of drug by the hydrogel over time.