When we take pills, we rarely consider the amazing facts that let us do so.

Do you ever consider that the pill we are taking is required to survive the hydrochloric and other acids in our stomach?  (Even if that pill is meant to travel around our body from the stomach, the “guts” of the pill have to survive our guts!)  And, if we need intestinal transfer (often where the transmission to our body is the best means of delivery), then the pill needs to be able to withstand all the enzymes in our intestines that were designed to break down proteins and then allow the dosage to pass through the mucus layer that protects the intestines from our enzymes and stuff we eat.

By now, you have probably figured out why we need those injectors to deliver insulin to our bodies. After all, diabetes is a prevalent disease given the states of our guts (and obesity).   Right now, these 40 million folks worldwide rely on using injectable insulin or an insulin pump.

Except injected insulin enters the bloodstream- and the proper dosage dissipates before it hits the liver.  Which means excess sugar is stored in our fat and muscle tissues, with a possibility of our manifesting hypoglycemia.  If we had orally delivered insulin, it would reach the liver directly,  yielding better glucose control and avoiding both hypo- and hyper-glycemia.

There are several approaches to developing an oral version of insulin.

First,  there’s NovoNordisk, which based its formulation using a delivery method developed by Merrion Pharmaceuticals.   The product was an oil and surfactant microemulsion, encapsulated in an enteric-coated gel.  But, in November 2017, they realized their product was unable to meet the body’s needs for adequate insulin, and ceased all further development.

Then, there’s Oramed, an Israeli company that hopes to finish its clinical trials and have the product in public use by 2023.  And, their product is viable for both type 1 (autoimmune- where the body destroys the insulin producing cells  in the liver) and type 2 (insulin resistant, requiring high dosages of insulin to be effective) diabetes.   Oramed’s approach is to encapsulate the insulin, along with added protease inhibitors, and some chelating agents.

Another approach is being investigated by Drs. S. Mitragotri and H. Wyss of Harvard’s Bioengineering department. They have found a way to surround insulin with an ionic liquid (composed of choline and geranate, which they call a “cage”; which not only protects the insulin, but thins the mucus, to afford better transport) and then surround that mess with a coating that is acid resistant.  Which means it should be possible for a pill containing insulin to traverse our guts and reach our bloodstream.

One of the key considerations of this formulation is that choline and geranic acid are considered to be safe by the FDA.  The FDA has a daily recommended dose for choline (an essential nutrient) and geranic acid (widely used food additive)

This new development was described in a publication in the Proceedings of the National Academy of Sciences in late June.  (A Banerjee, K Ibsen, T Brown, R Chen, C Agatemor, and S Mitragotri, Ionic liquids for oral insulin delivery)  The paper explains that the low dosage of insulin (3 to 10 units/kilogram) is all that is needed for it to be effective. Moreover, the formulaton is able to work (lowered blood glucose levels up to 45%) within the body for nearly 12 hours. ( This is far longer than injected insulin can be expected to provide benefits.). The product is stable for two months at room temperature and 4 months if refrigerated.

The team also plans to investigate what other biologics may be amenable to such a delivery system.

It probably won’t surprise you that they’ve formed a new company- Liquideon LLC (created under the laws of Delaware)- under whose rubric the product(s) will be sold. That seems all the rage nowadays when professors develop a potential new drug.

But, there’s already more competition!   Drs. Mary McCourt and Lawrence Mielnicki (and undergrad J. Catalano) from Niagara University have used a lipid vesicle to do almost the same thing.  Their patented concoction (called  a cholestosome®) is composed of natural lipid molecules (the smaller, building blocks of fats).  But, while a liposome would need a polymer coating, these don’t- the vesicles persevere the stomach acids, too.   And, once in the intestines, the body considers them “good stuff to absorb”.   Not surprisingly, either, McCourt has started her own firm, too- MMC Lipid Bioservices, Inc- to bring her product to market.