当前位置：
X-MOL 学术
›
J. Control. Release
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Bile acid transporter-mediated oral drug delivery
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-07-22 , DOI: 10.1016/j.jconrel.2020.07.034 Feiyang Deng 1 , You Han Bae 1
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-07-22 , DOI: 10.1016/j.jconrel.2020.07.034 Feiyang Deng 1 , You Han Bae 1
Affiliation
|
Bile acids are synthesized in the liver, stored in the gallbladder, and secreted into the duodenum at meals. Apical sodium-dependent bile acid transporter (ASBT), an ileal Na-dependent transporter, plays the leading role of bile acid absorption into enterocytes, where bile acids are delivered to basolateral side by ileal bile acid binding protein (IBABP) and then released by organic solute transporter OSTα/β. The absorbed bile acids are delivered to the liver via portal vein. In this process called “enterohepatic recycling”, only 5% of the bile acid pool (~3 g in human) is excreted in feces, indicating the large recycling capacity and high transport efficacy of ASBT-mediated absorption. Therefore, bile acid transporter-mediated oral drug delivery has been regarded as a feasible and potential strategy to improve the oral bioavailability. This review introduces the key factors in enterohepatic recycling, especially the mechanism of bile acid uptake by ASBT, and the development of bile acid-based oral drug delivery for ASBT-targeting, including bile acid-based prodrugs, bile acid/drug electrostatic complexation and bile acid-containing nanocarriers. Furthermore, the specific transport pathways of bile acid in enterocytes are described and the recent finding of lymphatic delivery of bile acid-containing nanocarriers is discussed.
中文翻译：
胆汁酸转运蛋白介导的口服药物递送
胆汁酸在肝脏中合成，储存在胆囊中，并在进餐时分泌到十二指肠中。顶端钠依赖性胆汁酸转运蛋白（ASBT）是一种回肠钠依赖性转运蛋白，在胆汁酸吸收进入肠上皮细胞中起主导作用，其中胆汁酸通过回肠胆汁酸结合蛋白（IBABP）递送到基底外侧，然后通过回肠胆汁酸结合蛋白（IBABP）释放到基底外侧。有机溶质转运蛋白 OSTα/β。吸收的胆汁酸通过门静脉输送到肝脏。在这个被称为“肠肝回收”的过程中，只有 5% 的胆汁酸库（人体内约为 3 g）通过粪便排出，这表明 ASBT 介导的吸收具有较大的回收能力和较高的运输效率。因此，胆汁酸转运蛋白介导的口服给药被认为是提高口服生物利用度的可行且潜在的策略。本文介绍了肠肝循环的关键因素，特别是ASBT摄取胆汁酸的机制，以及针对ASBT靶向的胆汁酸口服给药的发展，包括胆汁酸前药、胆汁酸/药物静电络合和胆汁酸/药物静电络合。含胆汁酸的纳米载体。此外，描述了胆汁酸在肠细胞中的具体转运途径，并讨论了含胆汁酸纳米载体的淋巴递送的最新发现。
更新日期：2020-07-22
中文翻译：
胆汁酸转运蛋白介导的口服药物递送
胆汁酸在肝脏中合成，储存在胆囊中，并在进餐时分泌到十二指肠中。顶端钠依赖性胆汁酸转运蛋白（ASBT）是一种回肠钠依赖性转运蛋白，在胆汁酸吸收进入肠上皮细胞中起主导作用，其中胆汁酸通过回肠胆汁酸结合蛋白（IBABP）递送到基底外侧，然后通过回肠胆汁酸结合蛋白（IBABP）释放到基底外侧。有机溶质转运蛋白 OSTα/β。吸收的胆汁酸通过门静脉输送到肝脏。在这个被称为“肠肝回收”的过程中，只有 5% 的胆汁酸库（人体内约为 3 g）通过粪便排出，这表明 ASBT 介导的吸收具有较大的回收能力和较高的运输效率。因此，胆汁酸转运蛋白介导的口服给药被认为是提高口服生物利用度的可行且潜在的策略。本文介绍了肠肝循环的关键因素，特别是ASBT摄取胆汁酸的机制，以及针对ASBT靶向的胆汁酸口服给药的发展，包括胆汁酸前药、胆汁酸/药物静电络合和胆汁酸/药物静电络合。含胆汁酸的纳米载体。此外，描述了胆汁酸在肠细胞中的具体转运途径，并讨论了含胆汁酸纳米载体的淋巴递送的最新发现。
京公网安备 11010802027423号