Abstract

Gastric-targeted drug delivery integrates the convenience of oral administration and local therapeutic action, aiming to improve precision while reducing systemic side effects. However, the extreme acidic environment, thick mucus and continuous peristalsis in the stomach present major challenges, resulting in inefficient or even ineffective gastric drug delivery. Here, we report a spatiotemporally controllable ship-shaped magnetic microneedle featuring a magnetic base and an array of pH-responsive conical microcavities loaded with drug powder for targeted gastric drug delivery. Benefiting from the magnetic- and pH-responsive functions, the microneedle remains stable in the gastric lumen, orients itself, penetrates the mucosa under a magnetic field, and rapidly releases the drug upon exposure to the near-neutral environment beneath the mucus barrier. Additionally, the conical microcavity design enables the microneedle to carry versatile drugs, including small molecules and biomacromolecules. In canine models, the microneedle exhibited flexible responsiveness to an external magnetic field. When evaluated in rabbit models using fluorescent molecules and insulin as model drugs, the microneedles exhibited effectively prolonged fluorescence retention and regulated blood glucose, respectively, without obvious side effects. This ship-shaped magnetic microneedle opens new horizons for efficient gastric drug administration and precise therapy.