On-skin glucose-biosensing and on-demand insulin-zinc hexamers delivery using microneedles for syringe-free diabetes management

Abstract

Patients who have diabetes must receive insulin administration two to three times every day via subcutaneous (SC) injection after measurement of blood glucose levels (BGLs) using lancet/blood-glucose meter with the side effects of pain and lipodystrophy. Achieving instrument-free glucose-biosensing and persistent glycaemic control in a painless and safe way is the ultimate goal of diabetes management. Here, we report the design of a microneedles (MNs) set comprising a glucose-biosensing microneedle patch (GBMP) and an insulin-delivery MP (IDMP). Once in the skin, the skin interstitial fluid (ISF) would diffuse into GBMP from epidermis to develop colour in abnormal glucose concentration which then quantified by smartphone. Subsequently, the IDMP composing of free insulin and biodegradable insulin-loaded glucose-responsive nanovesicles (IG-NVs) as an artificial on-skin pancreas, could be applied for hyperglycaemia-triggered insulin release to self-regulate BGLs and improve the health and quality of life for patients with type 1 and advanced type 2 diabetes. In chemically induced type 1 diabetic rats, the BGLs can be rapidly measured by GBMP and the BGLs can also be immediately reduced to and kept at normoglycaemic levels for up to 13 h by IDMP. The whole system permits the syringe-free diabetes management, avoiding both hyperglycaemia and hypoglycaemia.