Novel Hydrogel Delivery System Could Reduce Daily Diabetes Injections to Three Times a Year

Teaming up with Danish pharma giant Novo Nordisk, a research team at Stanford University recently developed an innovative drug delivery system that utilizes an injectable biomimetic hydrogel carrier along with GLP-1 receptor agonists commonly used in medications for both weight loss and blood glucose regulation to slowly release the drugs in experimental rats, extending the duration of drug action to approximately six weeks. 

With the research findings published in the journal Cell Reports Medicine, the team believes this novel approach may revolutionize the treatment of type 2 diabetes by allowing patients who would otherwise require daily or weekly injections to do so only once every four months (three times a year), making it easier for them to comply with physicians’ instructions and improving their health outcomes.

Related article: U.S.-German Joint Discovery May Spark Breakthrough in Diabetes Research

The Imminent Challenges of Surging Diabetic Population and Medication Adherence

Type 2 diabetes, which is closely linked to unhealthy lifestyle habits such as being overweight or obese, smoking, alcohol consumption, sugary and fatty diets, as well as inadequate physical activity, has gradually escalated to a global public health menace. According to a study published in July 2023 in The Lancet, as of 2021, there were approximately 529 million people living with diabetes worldwide, with an age-standardized prevalence rate of 6.1%, of whom over 90% suffered from type 2 diabetes. The study also estimated that this figure will exceed 1.3 billion by 2050, with the age-standardized prevalence rising to 9.8%. In an editorial published in the same journal in June, the author noted that by 2045, global healthcare expenditure related to diabetes could surge beyond $1 trillion, demonstrating a worrying trend together with a shocking description of diabetes as “a defining disease of the 21st century.”

Treating type 2 diabetes usually starts with changes in diet and lifestyle. However, long-term medications will be necessary in case such changes fail to manage the disease. Depending on patients’ conditions and the type of medication, physicians may decide how often patients should take their drugs, usually once a week, once daily, or twice daily. Yet, frequent injections may be burdensome and may lead to poor medication adherence, making it difficult for patients to manage their blood glucose levels, and may even trigger complications due to chronic hyperglycemia. 

Previous studies have found that less than half of Type 2 diabetics take their medication on time and as prescribed. Eric A. Appel, an Associate Professor in the Department of Materials Science and Engineering at Stanford and the principal investigator on the new hydrogel, got straight to the point, “Adherence is one of the biggest challenges in Type 2 diabetes management.”

PNP Hydrogel as a Novel Drug Carrier

Hydrogel is a unique material with biocompatibility and strong water-absorbing capacity. It is made up of hydrophilic polymers in a porous mesh structure, which can absorb water tens to thousands of times its original volume without dissolving. In recent years, hydrogels have attracted much attention in the biomedical field, and many studies have examined their potential as drug carriers in diverse applications, including wound care, nerve repair, cell therapy, and cancer therapeutics.

In this study, researchers designed a polymer-nanoparticle (PNP) hydrogel in which GLP-1 receptor agonists were formulated into the hydrogel, followed by injections into diabetic rats to test their drug release. This innovative preparation is characterized by its fluidity, which can be easily injected with an off-the-shelf needle, and the stability of the hydrogel, which can remain within the body for up to four months, which Prof. Appel explained to match the frequency of diabetic patients’ return visits to their physicians or endocrinologists. “Needing only three shots a year would make it much easier for people with diabetes or obesity to stick with their drug regimens,” he added.

Human Clinical Trials Within Reach

The study found that after the drug-loaded PNP hydrogel was injected subcutaneously into diabetic rats, a single shot could maintain consistent exposure to GLP-1 receptor agonists over 42 days in rats, corresponding to a once-every-4-months therapy in humans. The rats benefited from the GLP-1 receptor agonists’ actions in controlling blood glucose and body weight during this period, with comparable efficacy to conventional daily dosing. 

Stanford’s researchers are now able to adjust the duration of drug release as needed, ranging from a few days to six months. As the applications of hydrogel drug carriers expand to encompass small molecule drugs, proteins, vaccines, and even therapeutic cells like CAR-T cells, coupled with evidence that GLP-1 receptor agonists not only reduce weight and blood glucose levels but also cardiovascular disease risk, it is possible that PHP hydrogel carriers could be used in other medications or for treating a wider range of diseases in the future. 

The team’s next step is to conduct trials in pigs, whose skin and endocrine systems are much more similar to those of humans. If these trials work well, it is anticipated that human clinical trials could be conducted within a year and a half to two years.

Author

Richard Chau