Given the choice of taking a pill or injecting oneself with a needle, most of us would opt to regulate a chronic health condition by swallowing a pill. But for millions of people living with type 1 diabetes, a painful needle prick once or twice daily is the only option for delivering the insulin that their bodies cannot produce on their own.
Now, researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed an oral delivery method that could dramatically transform the way in which diabetics keep their blood sugar levels in check.
Not only does oral delivery of insulin promise to improve the quality of life for up to 40 million people with type 1 diabetes worldwide, it could also mitigate many of the disease’s life-threatening side effects that result from patients failing to give themselves required injections.
The research was published in the Proceedings of the National Academy of Sciences.
Insulin therapy, by injection just under the skin or delivered by an insulin pump, generally keeps the glucose levels of most diabetics in check. “But many people fail to adhere to that regimen due to pain, phobia of needles, and the interference with normal activities,” says senior author Samir Mitragotri, Hiller Professor of Bioengineering and Hansjorg Wyss Professor of Biologically Inspired Engineering at SEAS. “The consequences of the resulting poor glycemic control can lead to serious health complications.”
Finding a way to deliver insulin orally has been elusive; the protein does not fare well when it encounters the stomach’s acidic environment and it is poorly absorbed out of the intestine. The key to the new approach is to carry insulin in an ionic liquid comprised of choline and geranic acid that is then put inside a capsule with an acid-resistant enteric coating. The formulation is biocompatible, easy to manufacture, and can be stored for up to two months at room temperature without degrading, which is longer than some injectable insulin products currently on the market.
“It has been the holy grail of drug delivery to develop ways to give protein and peptide drugs like insulin by mouth, instead of injection,” says Mark Prausnitz, Regents’ Professor and J. Erskine Love, Jr. Chair in Chemical and Biomolecular Engineering at Georgia Institute of Technology. Prausnitz, who was not involved in the research, added: “This study shows remarkable results where insulin given by mouth in combination with an ionic liquid works about as well as a conventional injection. The implications of this work to medicine could be huge, if the findings can be translated into pills that safely and effectively administer insulin and other peptide drugs to humans.”
Orally ingested insulin would more closely mimic the way in which a healthy individual’s pancreas makes and delivers insulin to the liver, where up to 80 per cent is extracted and the rest is circulated through the bloodstream. It could also mitigate the adverse effects of taking injections over long period of time.
If further research progresses as hoped, the approach could be used for oral delivery of other proteins.