体内分布
化学
体内
药物输送
溶解度
乳状液
药代动力学
口服
胆碱
药理学
索拉非尼
药品
色谱法
生物化学
体外
内科学
医学
有机化学
生物技术
生物
肝细胞癌
作者
Yujie Shi,Zongmin Zhao,Yongsheng Gao,Daniel C. Pan,Alyssa K. Salinas,Eden E. L. Tanner,Junling Guo,Samir Mitragotri
标识
DOI:10.1016/j.jconrel.2020.03.018
摘要
Delivery of hydrophobic drugs is a significant challenge due to poor solubility and formulation difficulty. Here, we describe the potential of ionic liquids, in particular choline and geranic acid (CAGE), for oral delivery of a hydrophobic drug, sorafenib (SRF). CAGE provided excellent apparent solubility of SRF tosylate (> 500 mg/mL). Upon oral dosing in rats, CAGE increased peak blood concentrations of SRF by 2.2-fold. The elimination half-life of SRF was also increased by 2-fold and the mean absorption time was extended by 1.6-fold. Furthermore, SRF delivered by CAGE exhibited significantly different biodistribution compared to control formulations. Specifically, accumulation in lungs and kidneys improved 4.4-fold and 6.2-fold, respectively compared to control formulations. Mechanistic studies revealed that SRF-CAGE solution spontaneously formed a self-assembled structure (427 ± 41 nm), which is likely responsible for altered biodistribution in vivo. UPLC-MS studies confirmed the presence of choline-geranate species in blood indicative of micellar/emulsion structures which eventually dissociated into choline and geranic acid molecular species. These studies provide a simple, scalable strategy for oral delivery of hydrophobic drugs.
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