Advanced functional materials: a new direction of diabetes treatment intelligent bionic polymer Nanovesicles for improving sugar utilization

according to the latest report of the International Diabetes Institute (IDI) the number of patients with diabetes in the world will exceed 463 million in 2019 it is predicted that it will reach 578 million by 2030. As a traditional treatment subcutaneous injection of exogenous insulin can not achieve the gradient distribution of endogenous insulin from liver to peripheral under physiological conditions it is more difficult to achieve reasonable control of postprial blood glucose which will lead to peripheral hyperinsulinemia hypoglycemia other side effects. In the process of normal metabolism sugar intake from food will increase blood glucose stimulate islet β cells to secrete insulin rapidly act on peripheral tissues with appropriate concentration after accumulating in liver through hepatic portal vein. This glucose responsive release high concentration gradient between liver peripheral blood are very important for maintaining the physiological effect of insulin reducing side effects It's the meaning of life. Although the oral distribution of insulin in the gastrointestinal tract is very low the utilization of oral insulin is very complicated. Therefore an intelligent biomimetic nano carrier which can effectively absorb simulate the targeted distribution secretion behavior of endogenous insulin has a good prospect for the treatment of diabetes.

at present Gan Yong research group of Shanghai Institute of pharmacy Chinese Academy of Sciences has designed a kind of intelligent polymer Nanovesicles (PEP PMS) which can be used as gastrointestinal absorption barrier have the characteristics of targeting liver glucose responsive drug release. PEP PMS has a hollow structure which can load insulin efficiently. In high glucose environment PEP PMS vesicles can rupture rapidly release insulin. It is more important that PMS can maintain the change of blood glucose during postprial blood glucose PMS may have the ability to simulate the change of blood glucose release. In overcoming the barrier of intestinal epithelial cells PEP PMS can not only improve the cellular uptake of insulin but also avoid the degradation of intracellular lysosomes through GM1 mediated transport pathway on the surface of intestinal epithelium. Finally the carrier can be completely trans cellular. In vivo studies show that PEP PMS is mainly distributed in the liver after oral administration which can intelligently release insulin according to the concentration of glucose in the body form a concentration gradient distribution of insulin between liver peripheral tissue that simulates the characteristics of normal environment in vivo. In the model of type I diabetic rats PEP PMS showed a good effect of reducing blood glucose by releasing insulin in single multiple responses under the condition of hyperglycemia. Long term administration studies found that the level of liver glycogen in diabetic rats increased significantly which means that oral PEP PMS can not only control postprial blood glucose reasonably but also improve the utilization distribution of glucose in the body like normal body. At the same time PEP PMS has good biodegradability biosafety which will guarantee the application prospect of the nanocapsules. The researchers of

believe that this kind of intelligent biomimetic polymer Nanovesicles designed according to the body's own insulin secretion characteristics will provide a new technology method for the treatment of diabetes.

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