For hundreds of millions of diabetic patients, insulin injections have become an indispensable part of their daily lives.
Insulin can cause glucose to be taken up and metabolized by cells, which in turn reduces the concentration of glucose in the blood. However, under the existing ** model, diabetic patients usually need to inject insulin subcutaneously several times a day to maintain fasting blood glucose and postprandial blood sugar stability in accordance with daily dietary rules, which undoubtedly brings a huge burden to the daily life of diabetic patients. Once too much insulin is used, it can lead to hypoglycemia, posing a safety risk to patients.
So can we develop a preparation that can accurately control the release of insulin, so as to effectively control blood sugar for a long time with one injection?This simple wish of the common people is also a scientific frontier issue that the international scientific community has been aiming at for more than 100 years since the discovery of insulin.
A few days ago,The team of Professor Gu Zhen and researcher Wang Jinqiang from the School of Pharmacy and Jinhua Research Institute of Zhejiang University has developed a long-acting insulin preparation, which can intelligently sense the fluctuation of blood glucose, dynamically regulate the release rate of insulin, and realize the intelligent regulation of blood sugar for a long time.
A long-acting smart insulin preparation injected under the skin can quickly release insulin when blood sugar rises, stabilizing blood sugar.
The subcutaneous formulation, a white powdery complex of insulin and glucose-responsive polymers, has been shown to exhibit long-acting and intelligently responsive insulin release properties in large animal models based on pigs. Gu Zhen said that the team is promoting the application of clinical trials, and in the future, it may become a reality to safely and smoothly control sugar in the future with an insulin tube for a week or even longer.
The results were also published in the internationally renowned journal Nature Biomedical Engineering on December 6.
The research team (from right: Prof. Jinqiang Wang, Prof. Zhen Gu, PhD students Juan Zhang and Yanfang Wang).
Bionic human cells, one injection to stabilize blood sugar for a week
The cells of the human body can sense the concentration of glucose and regulate the secretion of insulin accordingly to adjust the rate of glucose metabolism in the body. However, people with diabetes are often unable to maintain normal blood sugar due to the loss of cells (type 1 diabetes) or insensitivity to islet secretion (type 2 diabetes).
Focusing on this scientific principle, the research team of Gu Zhen and Wang Jinqiang focused on breaking through the problem of how to quickly release insulin after a meal for a long time after a single dose, and slowly release insulin on an empty stomach through the function of bionic cells.
We have developed a novel complex consisting of gluconic acid-modified recombinant human insulin tightly combined with phenylboronic acid-modified polylysine. Gu Zhen introduced,This new complex acts as a "reservoir" of insulin when injected subcutaneously, facilitating long-term storage of insulin under the skin and rapid release when blood sugar rises.
Schematic diagram of complex formation and insulin-glucose-responsive release.
What's the magic of it?
This new complex is like an octopus, which firmly grasps the insulin with glucose through the suction cup (phenylboric acid), which changes the dilemma that the previous insulin storage preparation is easy to leak and does not last for a long time, and makes the complex slowly and continuously release a small amount of insulin under normal blood sugar conditions, so as to maintain the stability of basal blood sugar.
When the concentration of glucose in the blood increases, glucose can competitively bind to the "suckers" of the complex, which in turn rapidly releases insulin and returns blood sugar to the normal range.
This "smart" and long-lasting insulin dosage form has been successfully validated in laboratory animals, mice and pigs. Wang Jinqiang said: "In the existing experiments, we were able to maintain normal blood sugar for more than a week in 30 kg type 1 diabetes model pigs through a single dose, and there were no symptoms of hypoglycemia. ”
Changes in blood glucose levels and fluorescence of complex particles in diabetic piglets after long-acting smart insulin preparations**.
Drug capsules that come and go without a trace, leaving no traces in the body
There is often a risk that injected or implanted pharmaceutical preparations or devices containing biological materials will generally induce the formation of fibrous capsules. The formation of fibrous capsules can affect the function of the formulation and device, such as inhibiting the release of drugs.
The new complex developed by Gu Zhen and Wang Jinqiang's research team will quickly form a soybean-sized drug reservoir in the fat layer after subcutaneous injection, and with the slow release of insulin, the related polymer materials will also be quickly absorbed.
We're excited about this feature. It is precisely because of the unique properties of the materials we have developed and the dosage form that no fibroblast deposition is produced and therefore no cysts are formed. Wang Jinqiang introduced.
Professor John Buse, former Medical and Scientific Chair of the American Diabetes Association and collaborator, commented: "This is an exciting and important breakthrough in the development of new insulin, which has been sought for decades to make insulin more convenient and safer. ”
The first author of this study is Zhang Juan, a doctoral student in the School of Pharmacy of Zhejiang University, and the co-corresponding authors are Zhen Gu and Jinqiang Wang.
It is worth mentioning that this is another innovative progress made by the team formed by Gu Zhen since he returned to China more than three years ago. "Our team will continue to focus on clinical needs, adhere to the problem and product orientation, and look forward to more biomedical innovations benefiting the people as soon as possible. ”
Text reporter: Ke Yineng** provided by the interviewed team Today's editor: Hu Ya, student journalist group of the Rong ** Center of Zhejiang University, responsible editor: Zhou Yiying.
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