Magneto-Responsive Microneedle Robots for Intestinal Macromolecule Delivery.

Oral administration is the most convenient and commonly used approach for drug delivery, while it is still a challenge to overcome the complicated gastrointestinal barriers and realize efficient macromolecular drug absorption. Here, novel magneto-responsive microneedle robots are presented for efficient oral delivery of versatile macromolecules. These microneedle robots with three components of the magnetic substrate, the separable connection, and tips are generated by a Lego-brick-stacking-inspired multistage 3D fabrication strategy. With the assistance of commercial enteric capsule encapsulation, they can be taken orally and be released when entering the small intestine. Benefitting from their polarized magnetic substrate, the tips of the microneedle robots can orient to the small intestinal wall, overcome the barriers, insert into the tissue, and deliver encapsulated actives under specific magnetic fields. Besides, after the separable connection degrades, the tips can be left inside the tissue for continuous actives release, and the magnetic substrate can be excreted safely. Based on these features, the practical values of the microneedle robots are demonstrated by using them to orally deliver insulin and efficiently regulate the blood glucose of pigs. It is believed that the proposed microneedle robots can orally deliver diverse macromolecules and thus open a new chapter for oral administration.