Diabetes affects more than 400 million people worldwide and is a huge public health burden. People with diabetes produce little or no insulin, making it difficult for them to regulate their blood sugar levels. It has been more than 100 years since insulin was first applied in diabetes treatment in 1922, but insulin is difficult to administer orally and requires either an injection or an implanted pump. People with diabetes may need multiple daily insulin injections, and such frequent injections cause additional pain to the patient.
Furthermore, intensive insulin injections can also lead to inadequate compliance, tissue infection, and increased risk of hypoglycemia, which may lead to brain damage, epilepsy, loss of consciousness, and even death. Therefore, we urgently need a convenient and effective method for insulin management.
Oral insulin is the ideal way, but it is decomposed by the harsh environment in the stomach before it is absorbed into the gut and enters the blood. Moreover, insulin is a biological macromolecule, and the intestinal barrier formed by the tight epithelial cells and the mucus layer also further hinders insulin absorption.
Recently, Tu Yingfeng's team from Southern Medical University, together with Peng Fei from Sun Yat-sen University, published a research paper entitled: Micromotor Based Mini-Tablet for Oral Delivery of Insulin in the ACS Nano journal.
This study developed an orally available micromotor tablet to actively deliver insulin that can overcome the harsh gastrointestinal digestive environment and mucosal barrier system, and magnesium-based micromotors release hydrogen airflow at the site of the colon, enabling longer periods of blood glucose level control. Moreover, this technology can be used to improve the bioavailability of other biomacromolecules and has broad applications.
The colon, as part of the digestive system, has a thinner mucosal layer, more loose arrangement of epithelial cells and milder digestive conditions. Previous attempts at oral insulin administration, while protecting insulin from gastric acid with microcarriers or nanocarriers, which relied on the passive diffusion of insulin into the colonic epithelial cells, did not actually work well.
In this study, the insulin-loaded mini-tablets developed by the research team had tiny chemical "micromotors," and preclinical tests that demonstrated a safe and effective delivery of insulin to the colon.
To make the tablets, the team covered the magnesium particles with a layer of an insulin-containing solution and a liposome. They then mixed the particles with baking soda, pressed into tiny tablets approximately 3 mm in length, and then covered them with an esterified starch solution tAo protect the pills from gastric acid, bringing them up to the colon intact.
When the tablets is decomposed in the colon, the magnesium particles react with water to produce a flow of hydrogen bubbles, which, like micromotors, push insulin into the colonic mucosa and are absorbed.
Recently, magnesium-based micromotors have been widely used because they can continuously produce hydrogen bubbles under local body fluid, creating a strong driving force that enhances the uptake and absorption of insulin in the colon, thus improving the oral bioavailability of insulin, the team said.
The team on the diabetic rat model tested the oral insulin mini pill, found that it can significantly reduce the blood sugar levels of diabetic rats, triggered by the colon local water environment of the rapid movement of magnesium-based micro motor further enhance the colonic mucosa permeability and active delivery of insulin, the stability of blood sugar levels for more than 5 hours. Using this new insulin delivery technique, blood glucose levels can be maintained almost as low as the insulin injections.
While much further work needs to be done, the study reduced the timing of insulin administration and provided better compliance, demonstrating the feasibility of oral insulin and representing a concrete step in the development of traditional injectable drugs into oral drugs. Moreover, the magnesium-based micromotors are easily adjustable and biodegradable for promising applications in the biomedical field.
