Oral delivery of sorafenib through spontaneous formation of ionic liquid nanocomplexes

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.