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.

Keywords: Drug delivery; Insulin release; Phenylboronic acid; Poly(amidoamine) dendrimer.

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有效的糖尿病管理需要持续调节血糖水平，而葡萄糖响应性胰岛素递送系统为实现自主和精确的胰岛素释放提供了一种有前途的方法。为了提高葡萄糖敏感性，本研究提出了一种由聚（胺基胺）(PAMAM)树状分子与纳米结晶纤维素(NCC)核心功能化的4-羧基苯基硼酸(PBA)组成的混合型纳米载体。树状分子通过迈克尔加成和酰胺化反应的连续过程合成，利用胺基来调节PBA的pK_a以适应生理条件。该系统被分析了酸离解常数、胰岛素负载效率以及受控胰岛素释放情况。增加树状分子代数降低了酸离解常数，第三代产品与生理pH值相匹配。PAMAM-G3-PBA展示了74.2%的封装效率，在纯形式下释放了30%的胰岛素，在1 mg/mL时释放58%，在3 mg/mL葡萄糖浓度下释放60%。MTT试验结果显示了极佳的生物相容性，细胞存活率接近100%，直到200 μg/mL，仅在更高浓度时略有下降。这种纳米载体为葡萄糖响应性的胰岛素递送提供了可扩展且高效的途径，克服了糖尿病管理中的关键挑战。

关键词：药物递送；胰岛素释放；苯基硼酸；聚（胺基胺）树状分子。

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