RoboCap – The Robotic Capsule Designed to Improve Drug Delivery in the Gut
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Researchers have developed a robotic capsule designed to increase drug absorption by clearing mucus in the gut and depositing drugs directly on the intestinal surface. The study is published in Science Robotics.
The challenges of drug delivery in the intestine
The absorption of drugs taken by mouth can be limited by the physical conditions within the gastrointestinal (GI) tract. For example, the intestines are coated in layers of mucus designed to protect the layer of cells that line the intestine – the intestinal epithelium – from colonization by bacteria. Additionally, epithelial cells themselves are joined by cellular “tight junctions” that regulate the permeability of the epithelium, helping to prevent intestinal contents from leaking into the body.
These physical constraints mean that some drugs are not suitable to be taken in the form of capsules or pills, and must be taken parenterally (i.e., not by mouth or through the digestive tract). One example of this is insulin, a peptide hormone taken daily by millions of diabetics around the world to regulate their blood sugar levels. When taken orally, insulin has less than 1% bioavailability, meaning that it must be injected underneath the skin (subcutaneously), which can become a large burden for these patients. The antibiotic vancomycin is another example, which requires administration into a vein (intravenously, (IV)), a procedure that must be performed in a hospital setting.
What is bioavailability?
The bioavailability of a drug is a measure of how much of the drug is able to be absorbed to enter the circulation and reach the affected area.
Previous efforts to develop technologies to tackle problems surrounding drug delivery include using micro-stirring pills, mucus-penetrating liposomes and ultrasonic vibrations. However, the applications of these technologies are limited, as they must either be heavily optimized for each drug or are inconvenient for clinical use. In the current study from the Massachusetts Institute of Technology (MIT), the researchers aimed to overcome these obstacles and develop a robotic drug delivery device that could safely and effectively increase oral drug delivery and bioavailability.
Designing an effective robotic capsule
The motorized robotic capsule designed by MIT scientists – named the RoboCap – is the same size as a triple-zero capsule, or a large multivitamin pill. It features a “cargo hold” which stores the drug, as well as a gelatinous coating that protects tissue from damage and discomfort after swallowing. Once the RoboCap reaches the stomach, gastric acid degrades the gelatin coating, and the pH change after it passes into the small intestine dissolves a pH-sensitive membrane. This triggers the activation of the RoboCap by closing an electrical circuit within the capsule.
Once active, the RoboCap begins to spin, caused by an offset weight connected to a motor that generates the centripetal force required for the capsule to rotate. The capsule’s helical surface and studded texture make contact with the plicae (large circular folds of tissue) and villi (microscopic finger-like protrusions) on the surface of the intestine, which churns and clears away the mucus layer. The drug payload is then gradually released in this cleared area with each rotation of the RoboCap, depositing the drug directly onto the intestinal surface.
An in vivo study using pigs was then conducted to test the delivery of both vancomycin and insulin using the RoboCap. The small intestine of the anesthetized animals was isolated, and either a drug-loaded RoboCap was added, or a control treatment consisting of either a sham pill (vancomycin) or a spray (insulin). Results showed that the RoboCap increased the permeability of vancomycin into the tissue by over 20 times compared to the control, and significantly increased the concentration of vancomycin in the surrounding veins while the control samples had no effect. For insulin, delivery via the RoboCap significantly increased insulin levels in the blood and sharply decreased glucose levels compared to controls.
Technology Networks spoke to the study’s senior author Dr. Giovanni Traverso, assistant professor at MIT, and lead author and postdoctoral researcher Dr. Shriya Srinivasan about the development of the RoboCap. “Creating a micromachine that performs a variety of functions autonomously in the GI tract required the development of a robust system able to withstand the variation in environment and conditions present there. We overcame this by ideating various miniature mechanisms that could work synchronously to achieve the optimal rotation, wicking of mucus, etc. in the small intestine,” they explained.
The RoboCap remained active in the intestine for approximately 35 minutes. It is pushed along the gut by peristalsis, the rhythmic contractions of the circular muscles that move food along the GI tract. Further analysis of tissue from the in vivo trials showed that the RoboCap passed safely through the digestive systems of all 10 animals without any sign of inflammation, infection or damage to the intestinal epithelium.
Targeted RoboCap delivery and plans for clinical trials
Traverso and colleagues explain that this technology has the potential to be developed further by tuning the pH-sensitive activation membrane to activate at different pH levels. This will allow drug delivery to be targeted to different areas of the GI tract such as the stomach or colon which vary in pH.
The researchers also elaborated on some of their future plans for this device: “We will test the RoboCap on additional drugs and determine the best targets for clinical trials and seek partners for clinical translation. We are excited to see the impact this could have on serving populations that struggle with access to hospitals for medications requiring hospitalization. Additionally, we hope this will minimize the number of drugs that don’t make it to market due to poor bioavailability and improve the pharmaceutical industry’s ability to provide viable therapies.”
Dr. Giovanni Traverso and Dr. Shriya Srinivasan were speaking to Sarah Whelan, Science Writer for Technology Networks.
Reference: Srinivasan SS, Alshareef A, Hwang AV, et al. RoboCap: Robotic mucus-clearing capsule for enhanced drug delivery in the gastrointestinal tract. Science Robotics. 2022;7(70):eabp9066. doi: 10.1126/scirobotics.abp9066