Bile acid as an effective absorption enhancer for oral delivery of epidermal growth factor receptor targeted hybrid peptide
Bile acid as an effective absorption enhancer for oral delivery of epidermal growth factor receptor targeted hybrid peptide
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胆汁酸作为口服递送表皮生长因子受体靶向杂合肽的有效吸收促进剂
DOI：
10.1016/j.xphs.2017.12.012
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
K
中科院分区：
文献类型：
--
作者：
Gaowa;A.;Horibe;T.;Kohno;M.;Kawakami;K
本研究的目的是使用胆汁酸作为吸收促进剂来改善表皮生长因子受体靶向杂合肽的口服吸收。该肽的口服制剂通过阳离子肽和阴离子胆汁酸之间的静电相互作用形成。在Caco-2细胞和人胃癌移植瘤小鼠模型中比较研究了肽和肽/胆汁酸复合物的体外细胞渗透性和体内抗肿瘤作用。肽/胆汁酸复合物对Caco-2细胞单层的体外渗透性比单独的肽显著增强约5.0倍。此外，在用肽/胆汁酸复合物处理的体内小鼠异种移植物模型中，与单独的肽相比，显示平均肿瘤体积减少1.6倍。对血细胞计数、肝酶水平以及胃肠道组织和主要器官的组织病理学的初步安全性评价表明，肽/胆汁酸复合物未诱导任何急性毒性。这些结果表明，胆汁酸是一种有效的吸收促进剂，可提高表皮生长因子受体靶向杂合肽的口服生物利用度和生物活性。
The aim of this study was to improve the oral absorption of epidermal growth factor receptor–targeted hybrid peptide using bile acid as an absorption enhancer. The oral formulation of this peptide was formed through electrostatic interactions between the cationic peptide and anionic bile acid. Comparative studies ofin vitrocell permeability andin vivoantitumor effects of peptide and peptide/bile acid complex were performed in Caco-2 cells and in a xenograft mouse model of human gastric cancer. Thein vitropermeability of peptide/bile acid complex across Caco-2 cell monolayers was significantly enhanced to about 5.0-fold over those of peptide alone. Furthermore,in vivomouse xenograft model treated with peptide/bile acid complex showed a 1.6-fold reduction in the mean tumor volume as compared with the peptide alone. A preliminary safety evaluation of blood cells counts, liver enzyme levels, and histopathology of gastrointestinal tissues and main organs showed that the peptide/bile acid complex did not induce any acute toxicity. These results suggest that bile acid is an effective absorption enhancer for improving the oral bioavailability and bioactivity of epidermal growth factor receptor–targeted hybrid peptide.