A dabigatran etexilate phospholipid complex nanoemulsion system for further oral bioavailability by reducing drug-leakage in the gastrointestinal tract
A dabigatran etexilate phospholipid complex nanoemulsion system for further oral bioavailability by reducing drug-leakage in the gastrointestinal tract
复制标题
达比加群酯磷脂复合物纳米乳剂系统，通过减少胃肠道中的药物泄漏来进一步提高口服生物利用度。
DOI：
10.1016/j.nano.2017.08.009
复制
发表时间：
2018-06-01
影响因子：
5.4
通讯作者：
Zheng, Chunli
中科院分区：
文献类型：
--
作者：
Ge, Liang;He, Xinyi;Zheng, Chunli
达比加群酯（DE）在中性pH值下不溶，但由于质子化作用，在低pH值下可溶，这是市售DE产品生物利用度差的主要原因。在这里，我们首先开发了DE纳米乳液系统，并通过将DE封装到油相中来改善在模拟肠液中的溶解，但仍有35.8%的药物泄漏。此外，我们制备了DE-磷脂复合物（DE-PC），以提高DE的亲脂性和溶解性。所得DE-PC纳米乳显著（P < 0.05）减少药物渗漏和随后的沉淀。因此，与DE纳米乳和市售DE产品相比，DE-PC纳米乳的相对生物利用度分别增加至147.3%和606.6%。因此，目前开发的药物-磷脂复合物纳米乳液系统是一种有前途的药物递送系统，用于改善pH依赖性可溶性药物的口服生物利用度。(C)2017爱思唯尔公司All rights reserved.
Dabigatran etexilate (DE) is insoluble at neutral pH values but soluble at low pH values due to protonation, which is the major cause for the poor bioavailability of commercial DE products. Here, we first developed a DE nanoemulsion system and improved dissolution in simulated intestinal fluids by encapsulating DE into an oil phase, but 35.8% of the drug still leaked out. Further, we prepared a DE-phospholipid complex (DE-PC) to enhance lipophilicity and solubility of DE. The resulting DE-PC nanoemulsions significantly (P < 0.05) reduced drug leakage and subsequent precipitation. As a result, the relative bioavailability of DE-PC nanoemulsions increased to 147.3% and 606.6% compared to DE nanoemulsions and commercial DE products, respectively. Thus, the presently developed drug-phospholipid complex nanoemulsion system is a promising drug delivery system for improving the oral bioavailability of pH-dependent soluble drugs. (C) 2017 Elsevier Inc. All rights reserved.