Preparation of chitosan-based multifunctional nanocarriers overcoming multiple barriers for oral delivery of insulin
Preparation of chitosan-based multifunctional nanocarriers overcoming multiple barriers for oral delivery of insulin
复制标题
基于壳聚糖的多功能纳米载体的制备克服了胰岛素口服递送的多重障碍
DOI：
10.1016/j.msec.2016.08.083
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发表时间：
2017-01-01
影响因子：
7.9
通讯作者：
Yao, Juming
中科院分区：
文献类型：
--
作者：
Li, Lei;Jiang, Guohua;Yao, Juming
为了克服胰岛素口服给药的多重障碍，本研究设计并评价了以L-缬氨酸（LV，用作靶向配体以促进小肠吸收）和苯硼酸（PBA，用作葡萄糖响应单元）修饰的壳聚糖基多功能纳米载体。所得纳米载体对HT-29细胞表现出低细胞毒性，对蛋白质溶液表现出优异的稳定性。在体外考察了pH和葡萄糖对胰岛素释放的影响。分别在含胃蛋白酶的模拟胃液（SGF）和含胰酶的模拟肠液（SIF）中考察了负载胰岛素对消化酶的化学稳定性。激光共聚焦扫描显微镜观察HT-29细胞的摄取行为。糖尿病大鼠口服给药后，与皮下注射胰岛素相比，获得了有效的降血糖作用。本工作表明，L-缬氨酸修饰的壳聚糖基多功能纳米载体可能是一种有前途的口服给药胰岛素的药物输送载体。(C)© 2016 Elsevier B. V.版权所有。
To overcome multiple barriers for oral delivery of insulin, the chitosan-based multifunctional nanocarriers modified by L-valine (LV, used as a target ligand to facilitate the absorption of the small intestine) and phenylboronic acid (PBA, used as a glucose-responsive unit) have been designed and evaluated in this study. The resultant nanocarriers exhibited low cytotoxicity against HT-29 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. The chemical stability of loaded insulin against digestive enzyme were established in presence of simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing pancreatin, respectively. The uptake behavior of HT-29 cells was evaluated by confocal laser scanning microscope. After oral administration to the diabetic rats, an effective hypoglycemic effect was obtained compared with subcutaneous injection of insulin. This work suggests that L-valine modified chitosan-based multifunctional nanocarriers may be a promising drug delivery carrier for oral administration of insulin. (C) 2016 Elsevier B.V. All rights reserved.