4D Printing in Pharmaceuticals

The term four-dimensional (4D) printing refers to the fabrication via additive manufacturing (AM) of structures with the capability to shape transform over time under a predefined stimulus (e.g., temperature, pH, electric field, humidity). Since its introduction in 2013, 4D printing has been in rapid expansion in several fields, including smart textiles, autonomous and soft robotics, biomedical devices, electronics, and tissue engineering. Shape-changing, self-repairing, and self-assembly are some of the characteristics usually associated with 4D printing, highlighting that 4D printed structures are no longer static objects but programmable active structures that accomplish their function through a change in their physical and/or chemical properties over time when exposed to a predetermined stimulus. Here, AM acts as an enabling technology by allowing a precise arrangement of an exact amount of one or more stimulus-responsive materials in predefined positions, without any constraints on the geometric complexity. In the last few years, 4D printing has been exploited to develop increasingly sophisticated pharmaceutical and drug delivery systems, providing several advantages when compared with conventional fabrication approaches, such as (i) obtaining a highly controllable kinetic thanks to the smart properties and patterning of the involved stimulus-responsive material(s), (ii) achieving a time- and/or site-dependent drug release according to the shape-shifting of the structure after the sensing of a defined stimulus (e.g., change in pH or temperature, near-infrared lighting), and (iii) increasing the freedom to design systems able to settle, adapt, or remain and then release the conveyed drug in the target districts or move away from them. In this chapter, we aim to provide the reader with an overview of 4D printing, as an emerging and breakthrough fabrication technology. Then, relevant examples from the recent literature regarding the use of 4D printing for the development of pharmaceutical and drug delivery systems are presented and deeply discussed.