Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
University of Science and Technology of China, Hefei, 230026, P. R. China.
Macromol Biosci. 2019 Sep;19(9):e1900148. doi: 10.1002/mabi.201900148. Epub 2019 Jul 30.
Direct delivery of protein suffers from their in vitro and in vivo instability, immunogenicity, and a relatively short half-life within the body. To overcome these challenges, pH and glucose dual-responsive biodegradable nanogels comprised of dextran and poly(L-glutamic acid)-g-methoxy poly-(ethylene glycol)/phenyl boronic acid (PLG-g-mPEG/PBA) are designed. The cross-linked network imparted drug-loading efficacy of α-amylase up to 55.6% and hyaluronidase up to 29.1%. In vitro protein release profiles reveal that the release of protein is highly dependent on the pH or glucose concentrations, that is, less amount of protein is released at pH 7.4 or healthy blood glucose level (1 mg mL glucose), while quicker release of protein occurs at pH 5.5 or diabetic blood glucose level (above 3 mg mL glucose). Circular dichroism spectra show that the secondary structure of released protein is maintained compared to naive protein. Overall, the nanogels have provided a simple and effective strategy to deliver protein.
直接递送蛋白质会受到其体外和体内不稳定性、免疫原性以及在体内相对较短的半衰期的影响。为了克服这些挑战，设计了由葡聚糖和聚（L-谷氨酸）-g-甲氧基聚（乙二醇）/苯硼酸（PLG-g-mPEG/PBA）组成的 pH 和葡萄糖双重响应可生物降解纳米凝胶。交联网络赋予了 α-淀粉酶高达 55.6%和透明质酸酶高达 29.1%的载药效率。体外蛋白质释放曲线表明，蛋白质的释放高度依赖于 pH 或葡萄糖浓度，即在 pH 7.4 或健康血糖水平（1mg/mL 葡萄糖）下释放的蛋白质量较少，而在 pH 5.5 或糖尿病血糖水平（超过 3mg/mL 葡萄糖）下蛋白质释放更快。圆二色光谱显示，与天然蛋白质相比，释放的蛋白质的二级结构得以保持。总的来说，纳米凝胶为蛋白质的递供提供了一种简单有效的策略。
