Glucose-responsive nanogate of poly(methacrylic acid) brush-glucosamine network capping on the holes of chips for controlled insulin release

Background: Diabetes mellitus is a disease caused by deficient glycemic control by the pancreas that has caused serious health issues globally. Patients must inject insulin manually to stabilize their blood glucose levels (BGLs). Methods: A hole array was fabricated on a silicon wafer to graft poly(methacrylic acid) (PMAA) brushes from the silicon surface via atom transfer radical polymerization. Glucosamine (GA) was sequentially immobilized on the PMAA chains to obtain a P(MAA-GA) brush surrounding the hole edges on the silicon surface. After loading insulin inside the holes, biphenyl-4,4′-diboronic acid (DBA) was used to cross-link the P(MAA-GA) chains through the formation of boronate esters to cap the hole and block the release of insulin. Significant findings: The boronate esters were disassociated with glucose solution to open of the holes and the release of insulin, thus indicating a reversible association. The total amount of drug inside the chip was approximately 32.4 ± 1.8 g cm⁻², which could be released at a rate of approximately 107 ± 5.7 ng h⁻¹ cm⁻² at a glucose concentration of 1 g L⁻¹ for 270 h. Drug release was not significantly influenced by the presence of GA and amino acids, indicating excellent stability and selectivity of the chip.