Protein- and peptide-based medicines have great therapeutic potential, but delivering them effectively by mouth remains challenging. After oral administration, a drug must survive the acidic environment of the stomach, reach the appropriate region of the intestine, and establish effective contact with the intestinal mucosa. Conventional oral delivery systems largely rely on passive gastrointestinal transit followed by environmentally triggered drug release, making it difficult to simultaneously achieve precise targeting, stable mucosal contact, and controlled release timing.
To address this challenge, researchers developed the SMB-bot. The miniature robot can move and localize in the intestine under an external magnetic field and use microneedles to establish contact with the intestinal mucosa and release drugs at the target site, offering a new approach to targeted oral delivery of biologics.
The researchers integrated locomotion, drug loading, and mucosal interaction into a spherical robotic platform. The SMB-bot has a diameter of approximately 6.5 mm and can be loaded into a commonly used size-00 capsule. Its interior contains a magnetically responsive skeleton, while microneedle-based drug delivery units are arranged on the outer surface.
The microneedles feature a core–shell structure. The outer shell is made of Eudragit L100-55, which helps protect the payload under gastric conditions. Inside, the microneedle contains a drug or active pharmaceutical ingredient, together with a hyaluronic acid methacrylate (HAMA) hydrogel layer and a poly(vinyl alcohol) (PVA) sealing layer containing gelatin and iron oxide. This multilayer structure combines drug storage, tissue interaction, and magnetic responsiveness within the same microneedle.
Once the robot reaches the intestine, an external magnetic field can guide its movement toward the target region. Magnetic forces then help bring the microneedles into contact with and insert them into the intestinal mucosa, allowing the payload to be released locally. Unlike conventional carriers that mainly rely on passive gastrointestinal transport, this design introduces an active control step for guiding the drug carrier toward a desired location.
The researchers first evaluated the motion of the SMB-bot under an external magnetic field. By adjusting the magnetic-field frequency, they were able to control the robot's movement speed. At a fixed magnetic-field amplitude, its speed increased from approximately 25 to 180 mm/s, while the deviation between the actual and theoretical trajectories remained below 5%.
The team also investigated whether the microneedles could establish contact with and penetrate tissue. Experiments using tissue-mimicking models and ex vivo tissue showed that magnetic actuation could guide the robot toward the tissue surface and facilitate microneedle insertion under the combined effects of magnetic force and gravity.
Another key feature of the system was designed to prevent premature drug release. Insulin-loaded SMB-bots were first tested in simulated gastric fluid and then transferred to simulated intestinal fluid. Drug release was strongly suppressed under gastric conditions. After entering the intestinal environment, release did not immediately reach its maximum but instead showed a delay before increasing substantially. In the experiments, release began to accelerate after approximately 20 minutes in intestinal fluid and then increased rapidly over the following period.
The researchers could also adjust the insulin loading capacity by modifying the microneedle structure. In the porcine experiments, insulin delivered by the SMB-bot remained nearly undetectable during the first 20 minutes and then gradually increased, reaching a peak at approximately 80 minutes. By comparison, insulin levels rose earlier in the subcutaneous injection group. These findings indicate that the system can shift part of the drug exposure toward later time points, producing a delayed and sustained delivery profile.
The study combines biodegradable materials, magnetic actuation, and microneedle-based delivery into a miniature robotic platform capable of approaching the intestinal mucosa and releasing drugs locally. In vitro experiments and porcine studies demonstrated magnetic locomotion, mucosal insertion, and delayed drug delivery, providing preclinical evidence for a more actively controlled approach to oral biologic delivery.
However, the technology remains at an early preclinical stage. In the animal experiments, endoscopic and catheter assistance was used to deliver the robot to the target intestinal region. Therefore, the study does not yet demonstrate a fully autonomous process in which a swallowed capsule independently navigates to a deep intestinal target. Long-term biodegradation in vivo, magnetic navigation in deeper intestinal regions, long-term mucosal safety, and reproducible large-scale manufacturing also require further investigation.
Future studies will need to determine whether the platform can be adapted to biologics beyond insulin while improving navigation capability and manufacturing consistency. If these challenges can be addressed, a biodegradable miniature robot capable of moving, targeting, and releasing drugs could provide a more active and precise alternative to conventional oral drug-delivery systems.
Authors of the paper include Rong Tan, Xiong Yang and Yajing Shen.
This work was supported by the Hong Kong RGC General Research Fund (16213825).
The paper, "An Oral Biodegradable Spiny Milli-Ball Robot for Targeted Intestinal Delivery of Biologics with Delayed Onset and Sustained Action", was published in the journal Cyborg and Bionic Systems on Oct 16, 2026, at https://doi.org/10.34133/cbsystems.0716 .
