Ali Akbar, Saroj Saroj, Saha Sunita, Rakshit Tatini, Pal Suchetan
Department of Chemistry, Indian Institute of Technology-Bhilai, Raipur, Chhattisgarh492015, India.
Department of Chemistry, Shiv Nadar Institution of Eminence, Greater Noida, Uttar Pradesh201314, India.
ACS Appl Bio Mater. 2023 Feb 20;6(2):745-753. doi: 10.1021/acsabm.2c00951. Epub 2023 Jan 9.
Phenylboronic acid (PBA)-containing hydrogels (HGs), capable of glucose-responsive insulin release, have shown promise in diabetes management in preclinical studies. However, sustainable material usage and attaining an optimum insulin release profile pose a significant challenge in such HG design. Herein, we present the development of a straightforward fabrication strategy for glucose-responsive protein-polymer hybrid HGs (PPHGs). We prepare PPHGs by crosslinking polyvinyl alcohol (PVA) with various nature-abundant proteins, such as bovine serum albumin (BSA), egg albumin, casein, whey protein, and so forth, using formylphenylboronic acid (FPBA)-based crosslinkers. We showcase PPHGs with diverse bulk rheological properties that are appropriately modulated by the positions of aldehyde, boronic acid, and fluorine substitutions in the FPBA-crosslinker. The orthogonal imine and boronate ester bonds formed by FPBAs are susceptible to the acidic pH environment and glucose concentrations, leading to the glucose-responsive dissolution of the PPHGs. We further demonstrate that by an appropriate selection of FPBAs, glucose-responsive insulin release profiles of the PPHGs can be precisely engineered at the molecular level. Importantly, PPHGs are injectable, incur no cytotoxicity, and, therefore, hold great potential as smart insulin for in vivo applications in the near future.
含苯硼酸（PBA）的水凝胶（HG）能够实现葡萄糖响应性胰岛素释放，在临床前研究中已显示出在糖尿病管理方面的潜力。然而，在这种HG设计中，可持续的材料使用以及实现最佳胰岛素释放曲线构成了重大挑战。在此，我们展示了一种用于葡萄糖响应性蛋白质 - 聚合物杂化水凝胶（PPHG）的直接制备策略的开发。我们使用基于甲酰基苯硼酸（FPBA）的交联剂，通过将聚乙烯醇（PVA）与各种天然丰富的蛋白质（如牛血清白蛋白（BSA）、蛋清蛋白、酪蛋白、乳清蛋白等）交联来制备PPHG。我们展示了具有不同本体流变学性质的PPHG，这些性质可通过FPBA交联剂中醛基、硼酸和氟取代基的位置进行适当调节。由FPBA形成的正交亚胺和硼酸酯键对酸性pH环境和葡萄糖浓度敏感，导致PPHG发生葡萄糖响应性溶解。我们进一步证明，通过适当选择FPBA，可以在分子水平上精确设计PPHG的葡萄糖响应性胰岛素释放曲线。重要的是，PPHG可注射，无细胞毒性，因此在不久的将来作为体内应用的智能胰岛素具有巨大潜力。
