December 11, 2023

Animal cells have some things in common with plant cells, but one key feature we lack is a strong cell wall. While this provides structure to plants, scientists are also increasingly focusing on its use in new materials, cellulose technology and now insulin delivery.

Led by Henry Daniell of the Penn School of Dental Medicine, researchers have created a promising plant-based insulin containing three peptides naturally found in insulin that can also be taken orally.

As important as the genetic material inside, plant cell walls are key to drug efficacy. Their robustness protects insulin from the acids and enzymes of the upper gastrointestinal tract until the drug reaches the microbes in the gut, which do not release the insulin. From here, insulin travels through the gut-liver axis to its destination.

In tests on mice, plant-based insulin was able to regulate blood sugar within 15 minutes, comparable to naturally secreted insulin. Blood sugar levels dropped dramatically in mice treated with conventional insulin injections, leading to hypoglycemia.

“The risk of hypoglycemia is one of the biggest drawbacks of current delivery systems, which can even lead to coma,” Daniell said. “Our oral insulin contains all three proteins and is delivered directly to the liver. It acts like natural insulin and minimizes the risk of hypoglycemia.”

Current medications (e.g. injected via insulin pens) pose a risk of hypoglycemia, and the precise drug delivery provided by insulin pumps requires very expensive hardware. Current machines cost about $6,500 and have a lifespan of three to four years.

As for the drug itself, the complex process of genetic engineering is essentially a “gene gun” used to fire the human insulin gene through plant cell walls. These genes are integrated into the plant’s genome and selected over generations, bred from seeds that retain the blueprint so that all growing plants can be used to produce insulin.

Despite changes to this part of the genome, no adverse effects were seen in either the plants or animals tested, the study found.

With the genes intact, the lettuce can be freeze-dried, ground up and prepared for oral consumption.

Overview of Current Insulin Therapies and Upcoming Plant-Based Insulin Therapies
Overview of Current Insulin Therapies and Upcoming Plant-Based Insulin Therapies

The teams see another huge advantage to this approach to insulin therapy. Current clinical production requires culturing the hormone in bacterial or yeast cells under controlled laboratory conditions, storage and shipping.

“We’ve seen news reports of vaccine doses being destroyed because some countries don’t have the resources to refrigerate them throughout the process,” Daniel said. “That’s a huge cost. Using our method eliminates this post-production cost because we’ve repeatedly proven that the product is shelf-stable.”

While the results of the mouse study are very promising, it will be some time before this approach benefits many of the estimated 537 million people with diabetes. But the researchers are confident conducting larger trials, first in diabetic dogs and then in humans.

“Many dogs are diabetic, and owners have to inject insulin three times a day at home,” Daniell said. “We’ve done canine studies in the past with dogs with hemophilia or heart disease, and we know how to mix plant powders into their food and add some bacon flavor. They love it.”

That 2015 Research on Treating Hemophilia Improved lettuce has also shown the potential for effective, cheap and accessible phytotherapy against various diseases.

“With this delivery system, we change the whole paradigm, not just insulin,” he added. “I grew up in a developing country and saw people die because they couldn’t afford medicines or vaccines. For me, the affordability and global accessibility of healthcare is fundamental to my work. In this case, We’ve made insulin more affordable while dramatically improving it. Patients can get better medicine at a lower cost.”

The study was published in the journal biomaterials.

source: University of Pennsylvania