Simultaneous Diels-Alder click reaction and starch hydrogel microsphere production via spray drying

Herein, starch was used as a raw material to produce hydrogel microspheres via a strategy that combines spray drying and a Diels-Alder reaction. First, the starch was modified with N-maleoyl alanine and succinic acid amide. Second, starch hydrogel microspheres (SGPs) and drug-loaded hydrogel microspheres (5-Fu/SGPs) were produced by spray drying an aqueous solution of the as-prepared modified starch, forming chemical crosslinks via an in situ Diels-Alder reaction during the spray drying. The microspheres slowed the release rate of 5-Fu. In vitro cytotoxicity tests indicated that the SGPs are non-toxic for model human breast cancer cells; however, the 5-Fu/SGPs demonstrated clear cytotoxicity for human breast cancer cells. Taking into account the ease of the spray drying process and the good performance of the prepared microspheres, the strategy presented here has the potential to be applied to the green preparation of drug-loaded hydrogel microspheres.