Over the past several decades,there have been major advancements in the field of glucose sensing and insulin delivery for the treatment of type I diabetes mellitus.The introduction of closed-loop insulin delivery syst...Over the past several decades,there have been major advancements in the field of glucose sensing and insulin delivery for the treatment of type I diabetes mellitus.The introduction of closed-loop insulin delivery systems that deliver insulin in response to specific levels of glucose in the blood has shifted significantly the research in this field.These systems consist of encapsulated glucose-sensitive components such as glucose oxidase or phenylboronic acid in hydrogels,microgels or nanoparticles.Since our previous evaluation of these systems in a contribution in 2004,new systems have been developed.Important improvements in key issues,such as consistent insulin delivery over an extended period of time have been addressed.In this contribution,we discuss recent advancements over the last 5 years and present persisting issues in these technologies that must be overcome in order for these systems to be applicable in patients.展开更多
For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insuli...For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insulin delivery system yet could mimic both controlled basal insulin release and rapid prandial insulin release in response to real-time blood glucose changes. Here we reported an artificial insulin delivery system, mimicking physiological basal and prandial insulin secretion, to achieve real-time glycemic control and reduce risk of hypoglycemia. A phenylboronic acid(PBA)/galactosyl-based glucose-responsive insulin delivery system was prepared with insulin-loaded micelles embedded in hydrogel matrix. At the hyperglycemic state, both the hydrogel and micelles could swell and achieve rapid glucose-responsive release of insulin, mimicking prandial insulin secretion.When the glucose level returned to the normal state, only the micelles partially responded to glucose and still released insulin gradually. The hydrogel with increased crosslinking density could slow down the diffusion speed of insulin inside, resulting in controlled release of insulin and simulating physiological basal insulin secretion. This hydrogel-micelle composite insulin delivery system could quickly reduce the blood glucose level in a mouse model of type 1 diabetes, and maintain normal blood glucose level without hypoglycemia for about 24 h. This kind of glucose-responsive hydrogel-micelle composite may be a promising candidate for delivery of insulin in the treatment of diabetes.展开更多
基金supported in part by the Dean of the Cockrell School of Engineering at The University of Texas at Austin for the Institute for Biomaterials,Drug Delivery and Regenerative Medicinethe UT-Portugal Collaborative Research Program.
文摘Over the past several decades,there have been major advancements in the field of glucose sensing and insulin delivery for the treatment of type I diabetes mellitus.The introduction of closed-loop insulin delivery systems that deliver insulin in response to specific levels of glucose in the blood has shifted significantly the research in this field.These systems consist of encapsulated glucose-sensitive components such as glucose oxidase or phenylboronic acid in hydrogels,microgels or nanoparticles.Since our previous evaluation of these systems in a contribution in 2004,new systems have been developed.Important improvements in key issues,such as consistent insulin delivery over an extended period of time have been addressed.In this contribution,we discuss recent advancements over the last 5 years and present persisting issues in these technologies that must be overcome in order for these systems to be applicable in patients.
基金supported by the National Natural Science Foundation of China(51603105,51773099,51390483,91527306,21620102005)the Program for Changjiang Scholars and Innovative Research Team in University(IRT1257)
文摘For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insulin delivery system yet could mimic both controlled basal insulin release and rapid prandial insulin release in response to real-time blood glucose changes. Here we reported an artificial insulin delivery system, mimicking physiological basal and prandial insulin secretion, to achieve real-time glycemic control and reduce risk of hypoglycemia. A phenylboronic acid(PBA)/galactosyl-based glucose-responsive insulin delivery system was prepared with insulin-loaded micelles embedded in hydrogel matrix. At the hyperglycemic state, both the hydrogel and micelles could swell and achieve rapid glucose-responsive release of insulin, mimicking prandial insulin secretion.When the glucose level returned to the normal state, only the micelles partially responded to glucose and still released insulin gradually. The hydrogel with increased crosslinking density could slow down the diffusion speed of insulin inside, resulting in controlled release of insulin and simulating physiological basal insulin secretion. This hydrogel-micelle composite insulin delivery system could quickly reduce the blood glucose level in a mouse model of type 1 diabetes, and maintain normal blood glucose level without hypoglycemia for about 24 h. This kind of glucose-responsive hydrogel-micelle composite may be a promising candidate for delivery of insulin in the treatment of diabetes.
