An estimated 537 million people will have diabetes in 2021; According to the International Diabetes Federation (IDF), this number will increase to 643 million by 2030 and 783 million by 2045.
Diabetes can lead to several health problems and is a leading cause of death worldwide, along with cardiovascular disease (CVD), respiratory disease, and cancer.
Insulin, a hormone that regulates blood sugar levels, is injected to help manage diabetes. Insulin – in the form of a liquid solution or suspension – is injected under the skin (under the skin). Depending on the prescription, it can be taken several times a day. However, the inconvenience of using a needle and the cost of injectable insulin may prevent patient compliance. Research is underway to find alternatives to delivering insulin by inhalation, or by rectal, buccal, or oral routes.
Of these, oral delivery of insulin is the most convenient. However, because insulin is a peptide (a short chain of amino acids), it is acted upon by enzymes in the body that break down macromolecules in food into smaller molecules suitable for metabolism. When insulin is broken down by enzymes, its ‘bioavailability’ – the time it is available for use in the body – decreases.
Written by scientists from the Institute of Chemical Technology (ICT) in Mumbai, the human physiological system is a major barrier to insulin, limiting its bioavailability.
The paper, a literature review, focuses on oral insulin delivery strategies (OIDS), including nanoparticles, microparticles, nano-on-microparticles, hydrogels, tablets, capsules, enteral patches, and ionic liquids, to enhance the bioavailability of oral insulin.
A viable option
Oral insulin increases patient compliance and significantly lowers cost, but its development has been a challenge for the scientific community.
“Oral insulin is one of the most researched topics…Unfortunately, none of the products have reached commercial stage or success,” says Ratnesh Jain, associate professor of ICT. However, “such an option may be viable in the future,” he said Quantum.
Because insulin is sensitive to the acids and enzymes in our digestive system, drugs that break it down have no effect on the lining of the gut.
A strategy is to temporarily inhibit enzyme activity using alternative chemical agents.
“Sufficient bioavailability is necessary for drugs to work. We’re trying to suppress the acid/enzyme mix and at the same time create temporary pores for the peptides to pass through the stomach or intestinal barrier, so bioavailability can be increased,” he said.
The lining of the intestine also has various pores through which water, vitamins and nutrients can enter the blood. However, these pores are too small for drugs like insulin. Encapsulating agents (chemical agents) are used to increase the pore size.
These pores allow drugs to pass quickly from the gut into the bloodstream, along with a decrease in enzyme activity. This is known as the “Trojan horse” method.
“Oral peptide delivery is a major research topic in our lab,” Jain said.
In ICT, researchers have successfully used nanomaterials, chemicals, and excipients to increase the bioavailability of insulin.
“Formulation components are key to controlling this problem,” says Jain. Formulation components such as sugars, fatty acids, and polymers interact differently with acids and enzymes, and they interfere with the enzymes, creating temporary small pores in the barriers. “For this to work, many components need to be tested and sometimes the right ‘recipe’ needs to be created that will work for oral delivery of peptides. “We are still testing different prescriptions that will work for insulin,” he said.
So far, success has been limited. “One of the most successful strategies is the oral delivery of semaglutide, where the patented technology of the components of the formulation allowed to increase the bioavailability.” He added that there are drugs in various clinical stages of development.
An additional issue, he noted, is that early development is expensive and the Indian pharmaceutical industry can only fund late-stage developments. “Early-stage development requires government support,” says Jain. Another key issue is the need for a regulatory pathway for researchers.
“In our lab, we’ve created a regulatory pathway that fits the industry, and that’s one of the main reasons industry has come to collaborate with us,” he said.
We hope that this collaboration will soon allow thousands of diabetics to replace their insulin syringes with tablets.