Rocket‐Inspired Effervescent Motors for Oral Macromolecule Delivery

Abstract Oral administration is among the most convenient ways with good patient compliance for drug delivery; while it remains a challenge to achieve desirable bioavailability of most macromolecules due to the complex gastrointestinal barriers. Here, inspired by the structure and function of rocket, a novel micromotor delivery system is presented with scaled‐down rocket‐like architecture and effervescent‐tablets‐derived fuel for efficient oral macromolecule delivery by penetrating intestinal barrier. These rocket‐inspired effervescent motors (RIEMs) are composed of sharp needle tips for both loading cargoes and efficient penetrating, and tail wings for loading effervescent powders and avoiding perforation. When exposed to a water environment, the effervescent fuel generates intensive CO 2 bubbles to propel the RIEMs to move at high speed. Thus, the RIEMs with their sharp tip can inject into the surrounding mucosa for effective drug release. Furthermore, benefiting from their tail‐wing design, perforation can be effectively avoided during the injection process, ensuring the safety of the RIEMs in gastrointestinal active delivery. Based on these advantages, it is demonstrated that the RIEMs can efficiently move and stab into the intestinal mucosa for insulin delivery, exhibiting efficacy in regulating blood sugar glucose in a diabetic rabbit model. These features indicate that these RIEMs are versatile and valuable for clinical oral delivery of macromolecules.