4D printing of core–shell hydrogel capsules for smart controlled drug release

Personalized drugs, as well as disease-specific and condition-dependent drug release, have been highly desired in drug delivery systems for effective and safe therapies. Four-dimensional (4D) printing, as a newly emerging technique to develop drug capsules, displays unique advantages that can autonomously control drug release according to the actual physiological circumstances. Herein, core–shell structured hydrogel capsules were developed using a multimaterial extrusion-based 4D printing method, which consists of a model drug as the core and UV cross-linked poly(N-isopropylacrylamide) (PNIPAM) hydrogel as the shell. Owing to the lower critical solution temperature (LCST)-induced shrinking/swelling properties, the prepared PNIPAM hydrogel capsules showed temperature-responsive drug release along with the topography changes in the cross-linked PNIPAM network. The in vitro drug release test confirmed that the PNIPAM hydrogel capsules can autonomously control their drug release behaviors according to changes in ambient temperature. Moreover, the increased shell thickness of these capsules causes an obvious reduction in drug release rate, distinctly indicating that the drug release behavior can be well adjusted by setting the shell thickness of the capsules. The proposed 4D printing strategy pioneers the paradigm of smart drug release by showing great potential in the smart controlled release of drugs and macromolecular active agents.Graphic abstract