School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Carbohydr Polym. 2021 Jun 1;261:117873. doi: 10.1016/j.carbpol.2021.117873. Epub 2021 Feb 27.
The natural mucus cover has been a major obstacle to prevent enterocyte targeting particles from contact with the receptors. Thus, mucus penetration and intestinal targeting should be designed into one system. Based on the concept that biotin specifically recognizes epithelium receptors, enterocyte targeting muco-inert nanocomplexes were designed. Firstly, biotinylated chitosan (CS-Biotin) copolymers with different degree of substitution were synthesized and characterized. The nanocomplexes between CS-Biotin and insulin were prepared via self-assembly method. Thereafter, the nanocomplexes were fabricated by coating with various molecular weight hyaluronic acid (HA), which improved penetration efficiency in the mucus layer and small intestine in a HA molecular weight dependent manner. In vivo study indicated that hypoglycemic effect of the nanocomplexes was biotin modification degree and HA molecular weight dependent, with HA (200)-coated CS-Biotin21.8%/Insulin polyelectrolyte complex presenting the best performance. In conclusion, biotin decorated muco-inert nanocomplexes with HA coating are a promising platform for oral insulin delivery.
天然黏液层一直是阻碍肠细胞靶向粒子与受体接触的主要障碍。因此，应该将黏液穿透和肠道靶向设计成一个系统。基于生物素特异性识别上皮细胞受体的概念，设计了肠细胞靶向的黏液惰性纳米复合物。首先，合成并表征了不同取代度的生物素化壳聚糖（CS-Biotin）共聚物。通过自组装法制备了 CS-Biotin 与胰岛素之间的纳米复合物。此后，通过用各种分子量的透明质酸（HA）进行涂层来制备纳米复合物，这以 HA 分子量依赖性的方式提高了在黏液层和小肠中的穿透效率。体内研究表明，纳米复合物的降血糖作用取决于生物素修饰程度和 HA 分子量，其中 HA（200）涂层的 CS-Biotin21.8%/胰岛素聚电解质复合物表现出最佳性能。总之，具有 HA 涂层的生物素修饰黏液惰性纳米复合物是口服胰岛素递送的有前途的平台。
