Tablet with motor
The robocapsule for oral insulin delivery was tested on pigs
Yulia Panchenko, PCR.news
Oral drug delivery has many advantages, but the delivery of, for example, nucleic acids and proteins is associated with a number of difficulties associated with harsh conditions of the gastrointestinal tract and poor absorption. Absorption is difficult primarily because of the mucosa (mucus), which prevents the drug located in the intestinal lumen from reaching the epithelial layer. Researchers from the Massachusetts Institute of Technology and collaborators have developed a robotic drug delivery device that locally displaces mucus. The device was named RoboCap.
RoboCap is a plastic tablet the size of a multivitamin that carries a 342.6 mm3 load at one end. At the other end and on the surface there is a mechanism that allows him to "drill" the mucus. The device is covered with a gelatin shell, which initially hides its surface so as not to cause discomfort when swallowing. When passing through the stomach, the gelatin shell is destroyed.
The general scheme of work: A — activation of RoboCap in the intestine; B — the layers through which the drug will pass; C and D — the shape of the capsule; from E to H — the introduction of RoboCap into the intestinal wall. Drawings from the article by Srinivasan et al.
Upon reaching the small intestine, the pH change signals to the device that it's time to get to work. RoboCap starts to rotate and vibrate thanks to a small motor. There are also studs on the surface of the device that help it get through the mucus like a toothbrush. The rotation of the motor gradually destroys the section carrying the drug, releasing the latter. The device mixes the medium around itself, which contributes to the rapid dissolution of the drug.
RoboCap's work was initially evaluated on freshly extracted pig small intestine tissue. The study of the samples showed which hairpins of what length best displace the mucus, and also allowed to optimize the geometry of the device. Its chemical resistance was shown in a fluid simulating the fluid of the gastrointestinal tract. After 72 hours at 37°C, all capsules worked normally. At the same time, the device is practically not heated.
After that, an in vivo experiment was conducted on pigs under anesthesia, which were injected with a device carrying insulin or vancomycin (a peptide antibiotic). The concentration of vancomycin increased in the venous blood of pigs, which did not occur in controls who were given regular pills. Moreover, RoboCap significantly increases the bioavailability of insulin, which the authors showed by measuring blood glucose and insulin levels in pigs. Moreover, the glucose level began to change already 15 minutes after the introduction of the device; the changes continued throughout the observation period.
In all experiments with pigs, the device passed through the gastrointestinal tract without perforations or obstruction. There was no mucosal erosion, inflammation, infection or hematological complications, which was confirmed by endoscopy. The pathologist also did not notice any damage. The spent devices came out on their own.
According to the authors, RoboCap will allow oral administration of drugs that are currently administered through injections and inhalations. The researchers plan to continue optimizing the device. For example, they can be modified in such a way as to target the stomach or large intestine.
Article by Srinivasan et al. RoboCap: Robotic mucus-clearing capsule for enhanced drug delivery in the gastrointestinal tract is published in the journal Science Robotics.
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