Insulin nanoparticles may become an alternative to insulin injections for diabetic patients

Scientists at Nanyang Technological University, Singapore (NTU Singapore) have developed insulin nanoparticles that may one day become the basis for oral medicine, and an alternative to insulin injections for diabetic patients.

In a pre-clinical study, the NTU Singapore team fed insulin-containing nanoparticles to rats and found that insulin increased in their blood minutes later.

Insulin therapy is often an important part of treatment for diabetes, a metabolic disease that affects 422 million people globally. In Singapore, the number of diabetics is expected to grow to 1 million - almost a fifth of the population - in 2050.

Delivering insulin orally would be preferable over insulin jabs for patients because it causes less pain than jabs, and could thus lead to improved patient compliance. But oral dosage remains a challenge. As insulin is a protein, it gets broken down in the gastrointestinal tract before it can even reach the bloodstream to regulate blood glucose.

To overcome this challenge, the interdisciplinary team comprising scientists from NTU's School of Materials Science and Engineering and the Lee Kong Chian School of Medicine (LKCMedicine) designed a nanoparticle loaded with insulin at the core, then coated with alternating layers of insulin and chitosan, a natural sugar. Dosing is achieved by controlling the number of layers in the nanoparticle.

Through lab experiments using cell cultures and rat models, the team led by NTU principal research fellow Dr Huang Yingying, Associate Professor Yusuf Ali and former NTU Professor Subbu Venkatraman, demonstrated that this layer-by-layer coated nanoparticle is stable as it passes through the stomach into the small intestine with minimal insulin release, and is able to pass through the intestinal walls into the bloodstream. 

Insulin is a naturally occurring hormone that is critical for the regulation of blood glucose levels, especially after a meal.

In healthy individuals, insulin produced in the pancreas enters the bloodstream and is distributed to key metabolic organs. It instructs the liver, muscles, and fat cells to take up more glucose from the bloodstream and store it for future use.

At the same time, insulin nudges the liver to lower the rate of new glucose production, and altogether, these serve to effectively reduce blood glucose levels.

In contrast, diabetic patients do not produce sufficient insulin to meet the body demands. In serious cases, insulin needs to be given via a needle into the fatty tissue beneath the skin. From there, it goes into the general blood circulation throughout the body before travelling to the liver.

The NTU-developed oral insulin nanoparticle more closely mimics the route by which natural insulin enters the bloodstream from the liver, an important organ for controlling blood glucose levels.

Each of these nanoparticles is about 200nm in size - at least 1,000 times smaller than a pollen grain. Insulin is first loaded into the liposome, a tiny sphere at the core of the nanoparticle. The liposome is then coated with 11 alternating layers of insulin and chitosan of three different molecular weights, an approach that allows more insulin to be loaded.

When the insulin nanoparticle enters an acidic environment of the stomach, its layers start to repel each other, resulting in the slow release of insulin from the outermost layer, and leading inwards.

While it loses some insulin as it travels down the gastrointestinal tract, the nanoparticle has enough coatings that by the time it is transported through the intestinal wall and into the bloodstream, the insulin in the remaining layers and at the liposome, core is still intact.

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Endocrinology and Metabolism: Open Access
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