Scientists at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS, USA) have developed an oral delivery method that could dramatically transform the way in which diabetics keep their blood sugar levels in check.
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.
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 percent 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.
By encapsulating the insulin-ionic liquid formulation in an enteric coating, the team overcame the first obstacle, resisting breakdown by gastric acids in the gut. This polymer coating dissolves when it reaches a more alkaline environment in the small intestine, where the ionic liquid carrying insulin is released. The ionic liquid-borne insulin can be prepared in a one-step process that could be readily scaled up for inexpensive industrial production, making the cost of manufacturing the oral formulation easily manageable.
Senior author of the research is Samir Mitragotri, Hiller Professor of Bioengineering and Hansjorg Wyss Professor of Biologically Inspired Engineering at SEAS. The first author of the research, Amrita Banerjee, conducted the research while working as a postdoctoral fellow in Mitragotri’s lab, and is now an assistant professor at North Dakota State University (USA).
The researchers are optimistic that if all goes well, gaining approval for eventual clinical trials in humans will be made easier by the fact that the key ingredients in their ionic liquids – choline and geranic acid – are already considered safe. If further research progresses as hoped, the approach could be used for oral delivery of other proteins.