Researchers at the Massachusetts Institute of Technology (MIT) and Brigham and Women’s Hospital in Boston have designed a new type of pill that, once swallowed, can attach to the lining of the gastrointestinal (GI) tract and slowly release its contents. The tablet is engineered so that one side adheres to tissue, while the other side repels food and liquids that would otherwise pull it away from the attachment site.
Such extended-release pills could be used to reduce the dosage frequency of some drugs, the researchers say. For example, antibiotics that normally have to be taken two or three times a day could be given just once, making it easier for patients to adhere to their dosing schedules.
“This could be adapted to many drugs. Any drug that is dosed frequently could be amenable to this kind of system,” said Dr. Giovanni Traverso, one of the paper’s senior authors.
The device was described in the April 6 issue of Advanced Healthcare Materials.
During the past several decades, researchers have developed many types of materials that can be implanted in the body or attached to the skin for long-term drug release. To achieve similar, long-term drug release in the GI tract, the Boston team focused on mucoadhesives, which can stick to the mucosal linings of organs such as the stomach.
“The challenge with mucoadhesives is that the GI tract is a very rough and abrasive environment,” said lead author Young-Ah (Lucy) Lee, a technical assistant at MIT’s Koch Institute.
To overcome this challenge, the researchers created a dual-sided device, also called a Janus device after the two-faced Roman god. One side sticks to mucosal surfaces, while the other is omniphobic, meaning that it repels everything it encounters.
For the mucoadhesive side, the researchers used a commercially available polymer known as Carbopol, which is used industrially as a stabilizing or thickening agent. The omniphobic side of the device consists of cellulose acetate that the researchers textured so that its surface would mimic that of a lotus leaf, which has micro and nanoscale protrusions that make it extremely hydrophobic. They then fluorinated and lubricated the surface, causing it to repel nearly any material.
The researchers used a pill presser to combine the polymers into two-sided tablets, which can be formed into many shape and sizes. Drugs can be either embedded within the cellulose acetate layer or placed between the two layers.
Using intestinal tissue from pigs, the researchers tested three versions of the tablet: a dual-sided mucoadhesive tablet; a dual-sided omniphobic tablet; and the Janus version, with one mucoadhesive side and one omniphobic side.
To simulate the tumultuous environment of the GI tract, the researchers flowed a mix of food, including liquids and small pieces of bread and rice, along the tissue and then added the tablets. The dual-sided omniphobic tablet took less than one second to travel along the tissue, and the dual-sided mucoadhesive stuck to the tissue for only seven seconds before being pulled off. The Janus version stayed attached for the length of the experiment—approximately 10 minutes.
The researchers plan to do further tests in animals to help them fine-tune how long the tablets can stay attached; the rate at which drugs are released from the material; and the ability to target the material to specific sections of the GI tract.
In addition to delivering antibiotics, the two-sided tablet may help to simplify drug regimens for malaria or tuberculosis, among other diseases, Traverso said. The researchers may also pursue the development of tablets with omniphobic coatings on both sides, which they believe could help patients who have trouble swallowing pills.
“There are certain medications that are known to get stuck, particularly in the esophagus. It causes this massive amount of inflammation because it gets stuck, and it causes irritation,” Traverso said. “Texturing the surfaces really opens up a new way of thinking about controlling and tuning how these drug formulations travel.”
Source: MIT; April 6, 2016.
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