|10th April 2019
Taking inspiration from the leopard tortoise, an MIT research project sponsored by Novo Nordisk is aiming to deliver insulin orally with a pill that releases its medicine in the stomach lining, removing the need for injections. Dina Patel speaks to the lead author of the paper and MIT Chemical Engineering graduate student Alex Abramson and Ester Caffarel-Salvador, Postdoctoral Research Associate at MIT.
Alex: This device enables the delivery of all biologic drugs, not just insulin. We expect it could be used for nucleic acid delivery, protein, peptide, and antibody delivery. It has the capacity to transform how we deliver all of these drugs. A lot of companies will kill projects that involve macro molecule drugs requiring injections because they only offer an incremental improvement over an existing small molecule drug. They know people won’t want to take that injection over a pill that works almost as well, these macro molecule drugs which would have required an injection aren’t suitable for the market. We expect a huge amount of the macro molecule drug projects currently being killed by pharmaceutical companies could really benefit from this new technology for oral delivery.
Ester: We also anticipate that patients will not feel any pain from taking this pill. The gastrointestinal tract does not have pain receptors and, when tested in pigs, we didn’t observe any evidence of discomfort. We’ve looked closely into this and the safety of the device.
AA: When developing this pill, we created three new innovations. The first is the selfrighting system. I learned about a great mathematician in Hungary who had done a lot of research on the self-orienting nature of turtles and tortoises. We were inspired by the leopard tortoise – a tortoise found in eastern and southern Africa that can re-orient itself very easily based on its shape. It has a shell with a high, steep dome, allowing it to right itself when it rolls onto its back. Similarly, our pill has a shape close to the leopard tortoise shell and that makes it easy for it to reorient itself if it lands in a direction that isn’t facing the stomach tissue wall.
The second breakthrough was the sugarbased trigger, which ensures the pill doesn’t fire in the oesophagus when it’s ingested, instead it always fires in the stomach. The trigger senses the humidity in the gastrointestinal tract and that starts a timer. The sugar begins to dissolve and after about five minutes, it releases a compressed spring which pushes the drug into the tissue.
The last finding is the solid needle made almost completely out of insulin and other biological drugs. It allows us to deliver a clinically relevant dose. If we weren’t using a needle made almost completely out of drug, then we wouldn’t be able to deliver enough of the insulin.
AA: This has been my main focus for the past couple of years. It’s my thesis project and I helped coordinate the efforts between MIT and Novo Nordisk. My role consisted of developing the idea to make a self-orienting device and working on the amount of force necessary to inject the needle. I was also involved in making the sugar-based hydration mechanism and a solid dose of the needle.
ECS: The research began in August 2015. The lab is a very collaborative environment. We have a multidisciplinary team composed of technical assistants, professors, postdoctoral associates and many undergraduate students that visit for a term, the summer or even the whole year.
Alex and I have different areas of expertise. Alex is a chemical engineer and I am a bio-technologist and biochemist by training – our skills complement each other. I was involved in the formulation aspect of the prototype. I focused on tissue characterisation, on researching formulations and on the stability of the drugs. I tested the loading capacity of the device and optimised the analytical methods to quantify insulin. For example, I confirmed the insulin was still active when pressed into the device and ensured the properties didn’t change considering that we are submitting the insulin and other biologics to a high pressure during the fabrication process. Initially, this was a three-year collaboration project, but, now that we have this prototype, we have extended the collaboration.
|27th August 2020
Precision and personalised medicines are more than products, they are services in their own right. So, how should pharma approach this uncharted territory to ensure targeted therapies work for patients?