Given the choice of rejecting the drug dosage and pushing it through the meat in cold steel needles, most people choose pills. Comfort, portability and lack of stability on the skin have made the pill the most popular way to give drugs for most medical history. But not all drugs can survive a corrosive and restless journey from the stomach to the intestine and into the bloodstream. Antibodies, proteins: these molecules are too fragile. That's why you still have to get injections in the form of injections, and because many diabetics have to inject insulin twice a day to keep their blood sugar levels from becoming toxic.
But there might be another way, if you abandon all your assumptions about what makes the pill into a pill and inject it and apply a little technique to that question. Start with an insulin dose, dry with freezing and press in the form of a needle; You will need the form for the drug to enter the bloodstream. Put it in a pill about the size of a cranberry so you can swallow it. Take the time to reflect on charismatic reptiles and make some design adjustments. Voila, you have an injection version of insulin that can be swallowed. That's roughly the process of a research team led by the Massachusetts Institute of Technology, which today published its innovation in drug administration in the journal Science.
It's not just wild science experiments from the same lab that created this medieval work, which is full of microneedles, a few years ago. This work is part of a collaboration with Danish drug maker Novo Nordisk, the world's largest supplier of insulin. They hope to test capsules in humans in the next two or three years.
"The initial plan looks very promising," said Lars Fogh Iversen, senior vice president of global research technology at Novo Nordisk. "However, this is the first days and we have to work more, we haven't decided which molecule will be the right one for the first clinical trial." According to Fogh Iversen, the company is considering other fields besides diabetes, including obesity, hemophilia and growth hormone.
Pharmaceutical companies approached the MIT team for the first time in the fall of 2014, after the publication of its first attempt at a pack of needles in a pill. Intrigued by the possibility of offering a much easier and less painful way to remove their core products, Novo Nordisk began supporting the project in mid-2015, providing funding, materials and scientists. From the start, it meant that the technique could not only function in the laboratory. Only concepts that can increase commercial production are considered.
The first problem that must be solved by researchers is one orientation. The previous version of the group had microneedles arranged in 360 degrees to inject their insulin doses into the wall of the small intestine. In studies with pigs, it is injected well, but it is difficult to predict when and where in the intestine will occur. To achieve a faster and more reliable dose of action, the researchers decided to adjust their design to work exclusively in the stomach. But in that larger organ, the shape and design of the needle must change. They need to make sure that 100 percent of the needles come in contact with the lining of the stomach. It also implies that the pill cannot fall into free fall. "At first, we thought we could borrow from the Weeble Wobble," said Giovanni Traverso, a gastroenterologist at Brigham and Women's Hospital and Harvard Medical School and the paper's lead author. But the round-floor children's toys are designed to be pushed, they realize, "and we want something that will be fixed right after that."
Which brings us to the leopard turtle. Shell reptiles spend most of their days grazing on savannas in east and south Africa. But for certain groups of applied mathematicians, they are famous for the unique geometry of their dome-like skin. The shells make them the best people with their own rights in the reptile kingdom; They are basically a gömböc running. Alex Abramson, a graduate student at MIT in the project, used modeling software to make shellfish shaped capsules made of heavy steel at the bottom and biocompatible plastic lighters at the top. The result is a roly-poly-pill that must be adjusted autonomously.
Note the unique use of "needles". The new design is smaller, so it has room for fewer adhesive syringes. But at some point, the researchers realized that they only needed one, if they came out of insulin. Using a compression method similar to that of over-the-counter pills such as ibuprofen, they inject insulin into sharp, peg-shaped prints. The final product resembles a microscopic miniature javelin, although the author of the article prefers the term "millipostos".
The final challenge is to find a way to remove pure insulin capsules from a capsule with enough strength to penetrate the lining of the stomach and give the dose. And when the Eureka moment comes, kid, it's sweet. "We are looking for something common for each stomach and we find moisture," Abramson said. "We realize that some types of sugar break in the right way that releases a lot of kinetic energy when wet." Yes, they rotate the sugar barrier around the loaded steel spring and store it on the pill. where they cut a small vent to allow a few drops of gastric juice to enter, so that it dissolves sugar and releases the spring so that insulin is submerged in its final destination. Very cool
Even cooler, it seems to function quite well in testing with pigs. The researchers report that they have been able to reduce glucose levels in the blood of pig subjects and without side effects such as internal tears or gastric blocks at the output of pills. Traverso said the next project is to test capsules in larger animals, to understand what happens if they inject doses repeatedly day after day, because type 2 diabetes requires it to be beneficial. They also plan to add additional sensors to track where the pill is located and whether they ignore the dose or not. Both are important to convince regulators that capsules are safe and effective enough to replace insulin injections.
Drugs like insulin, which include not only hormones but also those made from DNA and antibody chains, are becoming more common, so researchers and pharmaceutical companies are looking for alternatives to inject them. "This shipping method developed by the Traverso team can apply to many drugs which, if they do not require hypodermic injection," said Mark Prausnitz, director of the Georgia Technology Center for Drug Design, Development and Delivery, who was not involved in the research. does not work with all drugs and patients.
Solving these questions can make it easier to treat big killers today with known drugs. It may also be important to resolve some of the challenges facing Crispr-based care in the future and many new types of vaccines, such as one for Ebola. .
