a College of Life Science , Anhui Normal University , Wuhu , P.R. China.
b School of Life Science and Biotechnology , China Pharmaceutical University , Nanjing , P.R. China.
Artif Cells Nanomed Biotechnol. 2018;46(sup3):S774-S782. doi: 10.1080/21691401.2018.1511575. Epub 2018 Oct 3.
In this paper, a new oral insulin formulation, insulin-loaded carboxymethyl-β-cyclodextrin-grafted chitosan nanoparticles (insulin/CMCD-g-CS NPs), was fabricated by ionic crosslinking technique. The therapeutic efficacy of new formulation was investigated in detail. Firstly, the CMCD-g-CS was synthesized by EDC-mediated esterification reaction. The prepared CMCD-g-CS exhibited favourable loading capacity and encapsulation efficiency of drug. The release experiment in vitro showed that the nanocarrier could efficiently protect encapsulated insulin at simulated gastric environment and release drug in the simulated colonic fluid. The insulin/CMCD-g-CS NPs effectively promoted drug internalization into Caco-2 cells and could reversibly open the tight junction between cells. The oral administration of insulin/CMCD-g-CS NPs could lastingly decrease blood sugar level in diabetic mice. The liver function study verified that the insulin/CMCD-g-CS NPs had not obvious toxicity to experimental mice. Therefore, the CMCD-g-CS could be an effective and safe oral insulin delivery carrier for future clinical application. A new biocompatible polysaccharide nanoparticle was fabricated as oral insulin delivery carrier for improving diabetic treatment.
本文采用离子交联技术制备了一种新型口服胰岛素制剂——载胰岛素羧甲基-β-环糊精接枝壳聚糖纳米粒（胰岛素/CMCD-g-CS NPs）。详细研究了新制剂的治疗效果。首先，通过 EDC 介导的酯化反应合成 CMCD-g-CS。所制备的 CMCD-g-CS 表现出良好的载药量和药物包封效率。体外释放实验表明，该纳米载体可以在模拟胃环境中有效保护包封的胰岛素，并在模拟结肠液中释放药物。胰岛素/CMCD-g-CS NPs 能够有效促进药物进入 Caco-2 细胞内，并能可逆地打开细胞间紧密连接。胰岛素/CMCD-g-CS NPs 的口服给药能够持久降低糖尿病小鼠的血糖水平。肝功能研究验证了胰岛素/CMCD-g-CS NPs 对实验小鼠没有明显的毒性。因此，CMCD-g-CS 可以作为一种有效的、安全的口服胰岛素传递载体，用于未来的临床应用。本文构建了一种新型生物相容性多糖纳米粒子作为口服胰岛素给药载体，以改善糖尿病的治疗效果。
