Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs

Abstract

Glucose-responsive insulin delivery systems that mimic pancreatic endocrine function could enhance health and improve quality of life for people with type 1 and type 2 diabetes with reduced β-cell function. However, insulin delivery systems with rapid in vivo glucose-responsive behaviour typically have limited insulin-loading capacities and cannot be manufactured easily. Here, we show that a single removable transdermal patch, bearing microneedles loaded with insulin and a non-degradable glucose-responsive polymeric matrix, and fabricated via in situ photopolymerization, regulated blood glucose in insulin-deficient diabetic mice and minipigs (for minipigs >25kg, glucose regulation lasted >20h with patches of ~5 cm 2 ). Under hyperglycaemic conditions, phenylboronic acid units within the polymeric matrix reversibly form glucose-boronate complexes that-owing to their increased negative charge-induce the swelling of the polymeric matrix and weaken the electrostatic interactions between the negatively charged insulin and polymers, promoting the rapid release of insulin. This proof-of-concept demonstration may aid the development of other translational stimuli-responsive microneedle patches for drug delivery.Diabetes-a chronic disease that often leads to severe secondary complications-affects over 425 million people around the world 1,2 . Insulin therapy is required for life in the setting of type 1 diabetes and is often used in type 2 diabetes with reduced islet β-cell function. It generally involves frequent monitoring of blood glucose levels and multiple subcutaneous injections daily or infusion to allow dose adjustment for safety and efficacy 1,3 . However, such treatment strategies are burdensome and often complicated by inadequate control and life-threatening hypoglycaemia resulting from miscalculated dose.

Fluid Nanocarrier for Insulin for Noninvasive Treatment of Diabetes Mellitus

“…Many reported techniques for improving the transdermal application have limitations [10][11][12][13][14][15][16]. The microneedles patches which based on a damage of the epidermis, can potentiates unhealable wounds by recurring application [35][36][37] where other approaches increase the treatment cost and need some skills through using special instruments.…”

“…Therefore, the formulations were applied in interval two days and the blood sugar level measured next day after application. These results are represented in gure 6 Figure 6: Blood sugar level during 2weeks in rats (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) after transdermal application of insulin every 2 days using DMSO solution (SR 7-10), MEIn2 (MER [11][12][13][14] and water solution (WR 15-18) Figure 6 shows no instantaneous lowering for blood sugar but gradually during the treatment over two weeks. Also, the signi cant decrease was recorded after 6 days using the DMSO solution where was relatively faster using MEIn2 which was recorded after 4 days.…”

“…Rheograms of prepared microemulsions by plotting the viscosity and shear stress against the shear rate. Blood sugar level during 2weeks in rats (7-18) after transdermal application of insulin every 2 days using DMSO solution (SR 7-10), MEIn2 (MER [11][12][13][14] and water solution (WR 15-18)…”

“…The idea of overcoming the stratum corneum to facilitate the transdermal penetration of insulin attracted many scientists [10][11][12][13]. Some of them preferred to pore it using micro-needles (10).…”

The Need for the Establishment of Biomedical Engineering (BME) as an Academic and Professional Discipline in the Philippines — A Quantitative Argument

“…With the large number of individuals who suffer from diabetes mellitus, there also exists a fair number of novel devices for insulin delivery in the market such as insulin pens and patch pumps. For instance, improved smart insulin delivery patches that monitor a patient's blood glucose and automatically inject insulin into the body whenever necessary are the subject of ongoing research and development [100]. Moreover, the field of biomedical engineering has paved the way for the creation of low-cost solutions, such as cost-effective insulin pumps for type-1 diabetic patients [101], and wearable devices, like V-GO®, that use less expensive insulin (e.g.…”