Abstract
A closed-loop system imitating the function of pancreatic cells, connected to microneedles (MNs) that automatically “release” insulin in response to the blood glucose (BG) levels would be highly satisfactory for improving the quality of life and health for diabetes patients. This paper describes an easy, fast and simple technique of coating a porous polymer layer on stainless steel (SS) MNs that release insulin in a glucose-responsive fashion. It was fabricated by sealing insulin, sodium bicarbonate (a pH-sensitive element [NaHCO3]) and glucose oxidase (glucose-specific enzymes [GOx]) into the pores of a porous polymer coating. Glucose can passively diffuse into the pores and become oxidized to gluconic acid by GOx, thereby causing a decrease in local pH. The subsequent reaction of protons with NaHCO3 forms carbon dioxide (CO2) which creates pressure inside the pores, thereby rupturing the thin polymer film and releasing the encapsulated insulin. Field emission scanning electron microscopy (FE-SEM) images displayed that upon the exposure of MNs to glucose-free phosphate buffer saline (PBS) with pH 7.4, the pores of the porous MNs were closed, while in MNs exposed to a hyperglycemic glucose level, the pores were opened and the thin film burst. These MNs demonstrated both in vitro (in porcine skin and PBS) and in vivo (in diabetic rats) glucose-mediated insulin release under hyperglycemic conditions with rapid responsiveness. This study validated that the release of insulin from porous MNs was effectively correlated with glucose concentration.
Highlights
Diabetes is one of the most universal persevering diseases, arising from a chronic metabolic disorder, in which glucose accumulates in the blood, causing a failure in the regulation of blood glucose levels [1]
It is intuitive that a closed-loop system, connected to MNs that automatically “release” insulin in response to the levels of blood glucose (BG), with the biocompatibility and flexibility of polymer materials, and an efficient approach of preparation, reduces the risk related to conventional treatment of diabetic patients
This study demonstrates a very quick, simple and robust method of fabricating a glucose-responsive insulin delivery system based on MNs
Summary
Diabetes is one of the most universal persevering diseases, arising from a chronic metabolic disorder, in which glucose accumulates in the blood, causing a failure in the regulation of blood glucose levels [1]. On-demand insulin delivery, desirable for diabetic patients, can be achieved with triggerable delivery systems In this way, blood glucose levels are maintained and the risk of hypoglycemia, caused by the release of excess drug, is reduced [16,19]. It is intuitive that a closed-loop system, connected to MNs that automatically “release” insulin in response to the levels of BG, with the biocompatibility and flexibility of polymer materials, and an efficient approach of preparation, reduces the risk related to conventional treatment of diabetic patients. Insulin release profiles were scrutinized at different glucose concentrations in vitro (in PBS and porcine skin) and in vivo in diabetic rats Both the results obtained in vitro and in vivo revealed that the fabricated porous coated MNs were highly glucose responsive. MNs samples were left at room temperature for two hours to allow the solvent to completely evaporate
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