Engineers at Stanford University have developed an injectable hydrogel depot technology that allows GLP-1 drugs to be administered once every four months, compared to repeated daily injections. Single-injection hydrogel-based medicines dramatically reduce the frequency of therapeutic interventions, significantly improve patients’ quality of life, and reduce complications of diabetes management. (Image credit: Andrea Ivana D’Aquino)
Materials engineers at Stanford University have developed a new hydrogel drug delivery system that changes daily or weekly injections of diabetes and weight management drugs such as Ozempic, Maunjaro, Trulicity, and Victoza to just once every four months. did. In a new study published on November 21, cell report medicineResearchers believe that such a system could significantly improve both diabetes and weight management, improve patient compliance, and help improve long-term health outcomes for people with type 2 diabetes.
All of these drugs work by mimicking the hormone glucagon-like peptide 1 (GLP-1). However, while good for diet and weight management, typical daily or weekly injections are a burden for many patients.
“Adherence is one of the biggest challenges in type 2 diabetes management,” says Dr. Roberts, associate professor of materials science and engineering at Stanford University and principal investigator of a new hydrogel that can slowly release diet-controlled drugs over many months. says Eric Appel. “If they only needed three injections a year, it would be much easier for people with diabetes and obesity to stick to their medication regimen.”
500 million people worldwide suffer from type 2 diabetes, including 130 million in the United States alone. The cost of treatment in the United States is estimated to exceed $400 billion each year. His GLP-1 drug, which was only recently introduced, has few side effects and reduces energy intake by increasing patients’ satiety, reducing hunger, and targeting other reward-related dietary effects. It is said to be a “miracle drug” that can provide significant control.
Novel nanocomposite hydrogel
The secret to hydrogels lies in the unique physical properties of the nanoparticles at their core. Hydrogels are not new. For example, many people today wear contact lenses made of hydrogels, which are designed to be tear-resistant and retain their shape. Appel’s hydrogels are designed using polymers and nanoparticles weakly bonded to each other so that they remain as a gel but slowly dissipate over time. Hydrogels are formed from a mesh of polymer chains and nanoparticles that hold drug molecules until the mesh dissolves and the drug is released.
“Our hydrogel dissolves, molecule by molecule, over many months, much like a sugar cube dissolves in water,” Appel explained. “I often say that the mesh is held in place by something like molecular Velcro, which sticks together very tightly but can be pulled apart easily.”
This new hydrogel, technically known as a polymer nanoparticle (PNP) hydrogel, has a Goldilocks “just right” quality of fluid-like flow, can be easily injected using off-the-shelf needles, and Gel-like stability makes it durable enough under environmental conditions. The body lasts for 4 months. GLP-1 drug molecules are formulated into a hydrogel and similarly administered over time as the hydrogel slowly dissolves and disappears.
Your doctor will inject a small amount of the drug-containing hydrogel, known as a “depot,” under your skin in a convenient place, such as your armpit. The key for engineers is to design a hydrogel that is small enough to make this depot comfortable and unnoticeable for the patient, yet large and durable enough to last a full four months. Appel believes his team achieved that degree of control.
“We chose the four-month period to match how often people actually see their doctors and endocrinologists and why we were so particular about the release period,” Appel said.
promising possibility
So far, the research team has tested the new drug delivery system in laboratory rats with high success. Appel said that in rats, his single injection of this hydrogel-based treatment improved blood sugar and weight control compared to daily injections of leading commercial drugs.
Although this particular hydrogel was specifically designed for GLP-1’s four-month screening regimen, the team was able to tailor the release period from a few days to more than six months, Appel said. . He added that such systems are used in other proteins, vaccines and even therapeutic cells, and there is evidence that GLP-1 drugs can reduce the risk of cardiovascular disease. All these signs indicate that this drug delivery system may be applicable to other drugs and other conditions.
“We’re also seeing very promising results in children with type 1 diabetes,” Appel said of his hopes for the future.
Tests will next be carried out on pigs, whose skin and endocrine systems are most similar to humans. If these trials go as planned, Appel could be able to conduct human clinical trials within 18 months to two years.
“At a minimum, we now have a pathway to long-term launches of GLP-1-based anti-diabetic and anti-obesity treatments that could have a beneficial impact on the management of type 2 diabetes, and perhaps other conditions as well.” ,” Appel said.
Other co-authors include postdoctoral researcher Andrea d’Aquino (first author); former graduate students Dr. Caitlin Maikawa (’21) and Dr. Catherine Casse (’22); PhD students Leslie Nguyen and Jerry Yang. graduate students Katie Lu, Ian Hall, and Carolyn Johns; Postdoctoral researcher Alexander Prosnitz. Undergraduate Researcher Enmian Zhang; and clinical veterinarian Sam Baker. Novo He is also a co-author of Nordisk researchers. Appel is a senior fellow at the Stanford Woods Institute for the Environment, a faculty fellow at Sarafan ChEM-H, and a member of Stanford Bio-X, the Heart and Vascular Institute, the Wu Tsai Human Performance Alliance, and the Institute for Maternal and Child Health. (MCHRI), Stanford Cancer Institute, and Wu Tsai Neuroscience Institute.
This research was funded in part by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases and a seed grant from the Stanford Diabetes Research Center.
