New Formulation to Deliver Insulin Orally

The primary treatment for Type 1 diabetes is daily insulin hormone injections. Type 2 diabetes usually requires treatment with insulin as the disease progresses. Researchers are now developing a new way to administer insulin orally with tiny vesicles that can deliver the medicine where it needs to go.

“A daily intramuscular injection regimen can be painful and tedious while daily subcutaneous injection, manually or via a pump, is a less efficient delivery mode. Orally available insulin would be a positive development in the treatment of diabetes. However, orally dosed insulin has not been developed yet due to insulin’s inabilities to survive both the acidic environment of the stomach, as well as be absorbed through the intestinal membrane,” said researchers led by Mary McCourt, PhD, of Niagara University.

The researchers have developed a neutral lipid-based vesicle called the Cholestosome^TM, which uses naturally occurring lipids for delivery of problematic therapeutics. In the current formulation, insulin dose is limited by solubility in the aqueous buffer prior to encapsulation.

The biggest obstacle to delivering insulin orally is ushering it through the stomach intact. Proteins such as insulin degrade before they get a chance to move into the intestines and then the bloodstream where they are needed.

Other efforts have been made to deliver insulin orally. One approach packages insulin inside a protective polymer coating to shield the protein from stomach acids; this is now in clinical trials. Another idea is inhalable insulin; despite good patient reviews, sales have lagged.

Using the patented Cholestosomes^TM, the Niagara University researchers have successfully encapsulated insulin. But their insulin package is unlike liposomes, which have been used as lipid-based drug carriers. Most liposomes need to be packaged in a polymer coating for protection. The Niagara University researchers just use simple lipid esters to make vesicles with the drug molecules inside, they explain.

Computer modeling showed that once the lipids are assembled into spheres, they form neutral particles resistant to attack from stomach acids. Drugs can be loaded inside, and the tiny packages can pass through the stomach without degrading. When Cholestosomes^TM reach the intestines, the body recognizes them as something to be absorbed. The vesicles pass through the intestines, into the bloodstream, and then cells take them in and break them apart, releasing insulin.

To pack the most insulin into the Cholestosomes^TM, the researchers determined the optimal pH and ionic strength of the drug-containing solution. They set out to develop higher dose insulin formulations for Cholestosome^TM encapsulation by examining parameters affecting solubility of insulin. They then moved the most promising candidates on to animal testing. Studies with rats showed that certain formulations of Cholestosomes^TM loaded with insulin have high bioavailability.

The researchers plan to further optimize the formulations, conduct more animal testing, and develop new partnerships to move forward into human trials.

The researchers presented their results at the 252nd National Meeting & Exposition of the American Chemical Society (Abstract "Formulation of insulin for oral dosing") in Philadelphia, PA, Aug. 24, 2016.