Smart glucose-responsive PAMAM dendrimers anchored on nanocrystalline cellulose for controlled insulin release

Effective diabetes management requires continuous blood glucose regulation, and glucose-responsive insulin delivery systems offer a promising approach for achieving autonomous and precise insulin release. In order to increase glucose sensitivity, this study presents a hybrid nanocarrier made of poly(amidoamine) (PAMAM) dendrimers with a nanocrystalline cellulose (NCC) core functionalized with 4-carboxyphenylboronic acid (PBA). The dendrimers are synthesized through a sequential process involving the Michael addition and amidation reactions, utilizing amine groups to adjust the pK_a of PBA to physiological conditions. The system is analyzed for acid dissociation constants, insulin-loading efficiency, and controlled insulin release. Increasing dendrimer generation lowers the acid dissociation constant, with the third generation aligning with physiological pH. PAMAM-G3-PBA demonstrates 74.2 % encapsulation efficiency, releasing 30 % insulin in pure form, 58 % at 1 mg/mL, and 60 % at 3 mg/mL glucose concentration. The MTT assay results confirm excellent biocompatibility, with nearly 100 % cell viability up to 200 μg/mL, showing a slight decline at higher concentrations. This nanocarrier offers a scalable and efficient approach for glucose-responsive insulin delivery, overcoming critical challenges in diabetes management.