Oral Delivery of Insulin Made Possible by Selenium Nanoparticles

By Benedette Cuffari, M.Sc.Sep 4 2017

Diabetes is a disease that affects the way in which the human body can produce or respond to insulin, which is an important hormone synthesized by the pancreas that regulates the conversion of sugar to energy.

Without proper production or utilization of insulin, diabetes can lead to a cascade of harmful effects including serious damage to the eyes, kidneys, nerves, as well as an increased chance of heart disease, stroke or limb amputation¹.

Insulin therapy remains one of the most effective treatment options for both type I and type II diabetes however, it can only be administered to patients through daily injections, making this an undesirable treatment for patients.

Aside from the frequent pain that is associated with the daily administration of subcutaneous injections of insulin, patients can also experience an allergic reaction, hyperinsulinemia, which describes excessive levels of insulin within the blood, lipodystrophy, an inability to produce fat surrounding the injection site and even hypoglycemia, a dramatic drop in blood sugar, as a result of a burst release of insulin following treatment.

Currently, therapeutic insulin cannot be taken orally, as it is a hormone that is made up of proteins that would be immediately digested and inactivated by gastric acids within the digestive system.

To combat this challenge, a group of Researchers from the College of Pharmacy at Jinan University in Guangzhou, China have developed selenium nanoparticles (SeNPs) for the oral delivery of insulin to effectively treat diabetes. Selenium (Se) is a trace element that plays an important role in a number of enzymes such as glutathione peroxidase (GSH-Px), which is an enzyme that plays an important antioxidant role within our immune system.

Individuals suffering from a number of diseases, primarily those that affect proper gastrointestinal function, such as diabetes, are often selenium deficient. To create the insulin-loaded SeNPs (INS-SeNPs) for this study, Researchers utilized an ionic cross-linking/in situ reduction technique by introducing Na₂SeO₃ into an insulin/chitosan complex. Glutathione (GSH) was then added to the complex solution, until the in situ formed INS-SeNPs reduced selenium and residual Na₂SeO₃ was eliminated by the system by dialysis against deionized water.

The Researchers studied the stability of the INS-SeNPs in stimulated gastric fluid (SGF) and simulated intestinal fluid (SIF). As compared to free insulin, which was ultimately degraded within 5 minutes in both SGF and SIF, INS-SeNPs exhibited a high stability against the digestive fluids, thereby ensuring the protection of insulin by the SeNPs. To study the antidiabetic efficiency of the INS-SeNPs, the Jinan Researchers performed in vitro studies to measure the release of insulin from the INS-SeNPs, as well as in vivo studies on normal Sprague-Dawley and type II diabetic Goto-Kakizaki rats.

Animals were given three different doses of INS-SeNPs of either 12.5, 25 or 50 IU/kg, in which plasma insulin concentration levels was compared to subcutaneous administration of insulin².

The Researchers found that the lower oral dose of INS-SeNPs elicited a long acting and prominent hypoglycemic effect, which confirms the ability of the INS-SeNPs to overcome digestive enzyme attacks while simultaneously promoting insulin absorption. By overcoming the two primary challenges that are associated with the effective oral delivery of insulin, the Jinan Researchers are hopeful in the potential of INS-SeNPs for future clinical application.

The estimated conversion of INS-SeNPs for human consumption would amount to 2 mg/day, which eliminates the possible toxic effects that could be associated with Se on the human body. While further studies must be conducted in order to complete the formulation process of this formulation, the Researchers are hopeful that their SeNP design can revolutionize the daily life of individuals who are struggling with their current diabetes treatment regimen.

Image Credit:

sciencepics/ Shutterstock.com

References:

1. “Diabetes” – MedlinePlus
2. “Selenium nanoparticles as versatile carriers for oral delivery of insulin: Insight into the synergistic antidiabetic effect and mechanism” W. Deng, Q. Xie, et al. Nanomedicine. (2017). DOI: 10.1016/j.nano.2017.05.002.

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