New Oral Insulin Delivery System Shows Promise

September 04, 1997

LAS VEGAS -- Researchers at Purdue University have developed an oral delivery method for insulin that may eliminate a diabetic's need to take insulin injections.

While the method has been shown to work only in the laboratory and in rats, and taking insulin orally is many years away, the researchers are cautiously optimistic that it may eventually be used to treat human diabetes.

The method also is the first oral insulin delivery system that has been shown, at least in rats, to be dose-dependent, where the amount of drug administered predictably changes blood glucose levels.

The delivery system currently is being tested further at Purdue, and the university has applied for a patent.

"The difficulty in delivering proteins such as insulin orally by tablet or capsule is that enzymes in the body, especially in the stomach, break down these proteins, rendering them inactive before they have a chance to work," says Nicholas Peppas, the Showalter Distinguished Professor of Chemical and Biomedical Engineering at Purdue.

"Our system can protect insulin from such enzymes and release the drug in a location where it can work, such as the small intestine or colon. If this oral method does indeed work in humans, it will revolutionize diabetes therapy, because it will eliminate insulin injections for many diabetics."

Peppas and doctoral student Anthony Lowman, who collaborated with scientists at Hoshi University in Japan, presented the research Sept. 10 at a meeting of the American Chemical Society in Las Vegas. Their work is supported by the National Institutes of Health and the Nagai Foundation of Tokyo.

Diabetes, a disease characterized by poor control of glucose levels in the blood, afflicts nearly 14 million Americans. It usually is attributed to inadequate secretion of the hormone insulin by the pancreas. When their blood glucose level gets too high, many diabetics must deliver insulin to the body by alternative methods, such as injections.

The drug-delivery system Peppas and Lowman designed with two Japanese collaborators relies on incorporating insulin into a gel-like material that Peppas developed. The gel is made primarily of a combination of polymers -- polymethacrylic acid, which has been used to make soft contact lenses, and polyethylene glycol, a nontoxic, noncarcinogenic substance used in many biomedical applications.

In a recent preliminary study with rats, which Lowman performed in Japan with scientists Tsuneji Nagai and Mariko Morishita, the researchers administered insulin-laden gel in a capsule to both healthy and diabetic animals. In all animals studied, they observed a significant lowering of blood glucose levels within two hours of giving the drug. In the case of the diabetic rats, blood glucose levels were reduced to normal levels for more than eight hours following a single oral dose.

"Other research groups studying similar delivery systems also have shown positive results in lowering blood glucose levels," Lowman says. "Our group is the first to show that we can vary the dosage to more predictably vary the hypoglycemic effect in both healthy and diabetic rats. Such dose-dependency allows us to better regulate how much of the drug to give to achieve the desired effect."

Lowman, who has accepted a professorial position at Drexel University, outlines how the Purdue system works:

In an acidic environment, the polymers in the gel interact in such a way as to shrink the pores of the gel, keeping insulin trapped inside, Lowman says. When the gel reaches a less acidic environment, such as in the small intestine, the gel swells and its pores open up, allowing the drug to diffuse into the surrounding tissue and eventually into the blood stream. The method by which the drug is actually delivered into the blood stream is under investigation, Peppas says.

The process by which the pores shrink and swell is called complexation, and Lowman devoted his doctoral research to understanding how the process works.

"The gel itself has molecular-sized pores that open and close in response to changes in the pH level, or acidity, of the environment," Lowman explains. "Each pore has strands of a polymer anchored to its sides, with the other end floating free in the pore. In the acidic environment of the stomach, these tethered chains reach across the pore and form temporary bonds with the other side, creating a kind of mesh, or crosslinking. The pore is not only physically blocked, but it also gets significantly smaller because the crosslinks pull it in tight."

When the gel passes into a less-acidic environment, the polymer chain immediately unlinks, the gel swells, and the pore size rapidly increases dramatically in size, releasing the drug.

The gel also has adhesive properties, which may contribute to its effectiveness in delivering drugs, Lowman says. "The gel gets more adhesive as it passes into the intestine so that it actually adheres to mucous in the intestine. More residence time probably helps the delivery of the insulin."

Sources: Anthony Lowman, (765) 494-3331; e-mail,
Nicholas Peppas, (765) 494-7944; e-mail,

Writer: Amanda Siegfried, (765) 494-4709; home, (765) 742- 2330; e-mail,

A.M. Lowman, N.A. Peppas, School of Chemical Engineering, Purdue University

Copolymer networks of poly(methacrylic acid) grafted with poly(ethylene glycol) (P(MAA-g-EG)) exhibit pH-dependent swelling behavior due to the formation/dissociation of interpolymer complexes. These complexes form in acidic media and serve as temporary, physical crosslinks and cause the gels to be in collapsed conformations. In solutions of pH greater than 5.0, the complexes dissociate due to ionization of the pendant acid groups resulting in a mesh size 3-5 times greater than in the collapsed state. These hydrogels are ideal for the oral delivery of peptides and proteins due to the large change in network structure over a small pH range.

The diffusion of insulin through swollen complexation gels was studied. The release of insulin from drug loaded P(MAA-g-EG) hydrogels was examined in pH=1.3 and 7.4 solutions. In simulated gastric fluid, pH=1.3, less than 5% of the insulin loaded into the system was released in two hours. However, when the gels were placed into solutions of pH=7.4, the remainder of the insulin was released in less than two hours. Diffusion coefficients for insulin in the complexed gels were two orders of magnitude less than those in the uncomplexed gels.

Purdue University

Related Insulin Articles from Brightsurf:

US Insulin prices 8 times higher than in other nations
Insulin list prices in the United States have increased dramatically over the past decade, with per person insulin spending doubling between 2012 and 2016.

A gatekeeper against insulin resistance in the brain
The brain plays a major role in controlling our blood glucose levels.

Sorting and secreting insulin by expiration date
Visualizing the age of insulin secreting granules in cells allowed researchers to investigate how cells' preference for secreting newer granules is disrupted in diabetes.

Researchers develop a new ultrafast insulin
Stanford researchers tested a new insulin drug in diabetic pigs and found that it was twice as fast-acting as traditional insulin.

Insulin signaling suppressed by decoys
The discovery of an insulin 'decoy' molecule from the lab of Matthew Gill, PhD, in Florida shakes up understanding of insulin signaling, with implications for diabetes, longevity and aging research.

New mechanism for dysfunctional insulin release identified
In a new study, researchers at Uppsala University have identified a previously unknown mechanism that regulates release of insulin, a hormone that lowers blood glucose levels, from the β-cells (beta cells) of the pancreas.

Type 2 diabetes is not just about insulin
Obesity, by promoting the resistance to the action of insulin, is a major risk factor of diabetes.

The insulin under the influence of light
By understanding how the brain links the effects of insulin to light, researchers (UNIGE) are deciphering how insulin sensitivity fluctuates according to circadian cycles.

Does insulin resistance cause fibromyalgia?
Researchers led by a team from The University of Texas Medical Branch at Galveston were able to dramatically reduce the pain of fibromyalgia patients with medication that targeted insulin resistance.

Insulin insights
Insulin triggers genome-wide changes in gene expression via an unexpected mechanism.

Read More: Insulin News and Insulin Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to