Multicompartment Tubular Micromotors Toward Enhanced Localized Active Delivery

Abstract

A tubular micromotor with spatially resolved compartments is presented toward efficient site-specific cargo delivery, with a back-end zinc (Zn) propellant engine segment and an upfront cargo-loaded gelatin segment further protected by a pH-responsive cap. The multicompartment micromotors display strong gastric-powered propulsion with tunable lifetime depending on the Zn segment length. Such propulsion significantly enhances the motor distribution and retention in the gastric tissues, by pushing and impinging the front-end cargo segment onto the stomach wall. Once the micromotor penetrates the gastric mucosa (pH ≥ 6.0), its pH-responsive cap dissolves, promoting the autonomous localized cargo release. The fabrication process, physicochemical properties, and propulsion behavior are systematically tested and discussed. Using a mouse model, the multicompartment motors, loaded with a model cargo, demonstrate a homogeneous cargo distribution along with approximately four-fold enhanced retention in the gastric lining compared to monocompartment motors, while showing no apparent toxicity. Therapeutic payloads can also be loaded into the pH-responsive cap, in addition to the gelatin-based compartment, leading to concurrent delivery and sequential release of dual cargos toward combinatorial therapy. Overall, this multicompartment micromotor system provides unique features and advantages that will further advance the development of synthetic micromotors for active transport and localized delivery of biomedical cargos.

Keywords: active delivery; biomedical cargos; gastric mucosa; gastric-powered propulsion; localized cargo release; pH-responsive materials; tubular micromotors.