Self-assembled glycol chitosan nanogels containing palmityl-acylated exendin-4 peptide as a long-acting anti-diabetic inhalation system
Self-assembled glycol chitosan nanogels containing palmityl-acylated exendin-4 peptide as a long-acting anti-diabetic inhalation system
复制标题
DOI：
10.1016/j.jconrel.2012.05.029
复制
发表时间：
2012-08-10
影响因子：
10.8
通讯作者：
Youn, Yu Seok
中科院分区：
文献类型：
--
作者：
Lee, Juho;Lee, Changkyu;Youn, Yu Seok
采用自组装技术制备了含有棕榈酰化exendin-4（Ex 4-C16）的可吸入脱氧胆酸修饰乙二醇壳聚糖（DOCA-GC）纳米凝胶，并对其进行了理化表征。使用红外成像系统监测DOCA-GC纳米凝胶的肺沉积，并在2型糖尿病db/db小鼠中肺部施用后评价由Ex 4-C16负载的DOCA-GC纳米凝胶引起的低血糖。分别在人肺上皮细胞（A549和Calu-3）和db/db小鼠中检查DOCA-GC纳米凝胶诱导的细胞毒性和肺组织学。结果表明，所制备的DOCA-GC纳米凝胶呈球形，粒径约为220 nm，结构致密。尽管Ex 4-C16（50.9 +/-7.8%）掺入DOCA-GC纳米凝胶中显著低于Ex 4（81.4 +/-4.9%），但Ex 4-C16从DOCA-GC纳米凝胶的释放相对于Ex 4大大延迟。DOCA-GC纳米凝胶在肺部给药后迅速沉积，并在肺部保留约72小时。此外，在db/db小鼠中，吸入Ex 4-C16纳米凝胶的低血糖持续时间远大于Ex 4纳米凝胶的低血糖持续时间。DOCA-GC纳米凝胶的细胞毒性结果被认为是可接受的，并且施用纳米凝胶的小鼠肺的组织组织学与对照肺相比没有显示出任何显著差异。作者认为，Ex 4-C16 DOCA-GC纳米凝胶为治疗2型糖尿病提供了一种长效吸入给药系统。(c)2012爱思唯尔有限公司版权所有。
Inhalable deoxycholic acid-modified glycol chitosan (DOCA-GC) nanogels containing palmityl acylated exendin-4 (Ex4-C16) were prepared by self-assembly and characterized physicochemically. The lung deposition of DOCA-GC nanogels was monitored using an infrared imaging system, and the hypoglycemia caused by Ex4-C16-loaded DOCA-GC nanogels was evaluated after pulmonary administration in type 2 diabetic db/db mice. The cytotoxicities and lung histologies induced by DOCA-GC nanogels were examined in human lung epithelial cells (A549 and Calu-3) and db/db mice, respectively. Results showed that the DOCA-GC nanogels prepared were spherical and compact and had a diameter of similar to 220 nm. Although the incorporation of Ex4-C16 (50.9 +/- 7.8%) into DOCA-GC nanogels was significantly lower than that of Ex4 (81.4 +/- 4.9%), the Ex4-C16 release from DOCA-GC nanogels was greatly delayed vs. Ex4. DOCA-GC nanogels were deposited rapidly after pulmonary administration and remained in the lungs for similar to 72 h. Furthermore, the hypoglycemic duration of inhaled Ex4-C16 nanogels was much greater than that of Ex4 nanogels in db/db mice. Cytotoxicity results of DOCA-GC nanogels were considered acceptable, and the tissue histologies of mouse lungs administered nanogels did not show any significant difference vs. control lungs. The authors believe that Ex4-C16 DOCA-GC nanogels offer a long-acting inhalation delivery system for treating type 2 diabetes. (c) 2012 Elsevier B.V. All rights reserved.