A self-powered controllable microneedle drug delivery system for rapid blood pressure reduction

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.

A patch with the capability of avoiding wound infection and promoting tissue remolding is of great value for wound healing. In this paper, we develop a biomass chitosan microneedle array (CSMNA) patch integrated with smart responsive drug delivery for promoting wound healing. Chitosan possesses many outstanding features such as the natural antibacterial property and has been widely utilized for wound healing. Besides, the microstructure of microneedles enables the effective delivery of loaded drugs into the target area and avoids the excessive adhesion between the skin and the patch. Also, vascular endothelial growth factor (VEGF) is encapsulated in the micropores of CSMNA by temperature sensitive hydrogel. Therefore, the smart release of the drugs can be controllably realized via the temperature rising induced by the inflammation response at the site of wounds. It is demonstrated that the biomass CSMNA patch can promote inflammatory inhibition, collagen deposition, angiogenesis, and tissue regeneration during the wound closure. Thus, this versatile CSMNA patch is potentially valuable for wound healing in clinical applications.

Hypertension and chronic kidney disease (CKD) are closely interlinked pathophysiologic states, such that sustained hypertension can lead to worsening kidney function and progressive decline in kidney function can conversely lead to worsening blood pressure (BP) control. The pathophysiology of hypertension in CKD is complex and is a sequela of multiple factors, including reduced nephron mass, increased sodium retention and extracellular volume expansion, sympathetic nervous system overactivity, activation of hormones including the renin-angiotensin-aldosterone system, and endothelial dysfunction. Currently, the treatment target for patients with CKD is a clinic systolic BP < 130mm Hg. The main approaches to the management of hypertension in CKD include dietary salt restriction, initiation of treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic therapy. Uncontrolled hypertension can lead to significant cardiovascular morbidity and mortality and accelerate progression to end-stage kidney disease. Although intensive BP control has not been shown in clinical trials to slow the progression of CKD, intensive BP control reduces the risk for adverse cardiovascular outcomes and mortality in the CKD population.