Biocompatible diimidazolium based ionic liquid systems for enhancing the solubility of paclitaxel

Paclitaxel (PTX) is a crucial medication employed in the treatment of various cancers, and its limited solubility has been a persistent clinical hurdle. Ionic liquids (ILs), considered as "green solvents", possess remarkable attributes such as exceptional miscibility, tailorable properties, and versatility. These properties have ushered in a revolution in the realm of biomedicine, particularly in addressing the solubility challenges of poorly soluble drugs. In this work, low-toxicity diimidazolium based ILs were introduced into a PTX dissolution system for the first time. Compared to mono-imidazolium based ILs, diimidazolium based ILs exhibited lower in vitro cytotoxicity and the substitution of Cremophor EL (CrEL) with biocompatible [C10(MIM)2][Br]2 and water resulted in lower cytotoxicity at a certain concentration. Furthermore, [C10(MIM)2][Br]2 could effectively improve the solubility of PTX, and this enhancement was strongly correlated with the length of the carbon chain in the cation and the IL concentration. Significantly, the [C10(MIM)2][Br]2-based dissolution system demonstrated the capability to attain a PTX content that is on par with the widely used commercial drug Taxol. Besides, the [C10(MIM)2][Br]2-PTX complex displayed excellent physical stability for a long period of time, with no significant change of PTX concentration in the solution. Additionally, various interactions existed between [C10(MIM)2][Br]2 and PTX, encompassing hydrophobic interactions, pi-pi stacking, CH-pi interactions, and hydrogen bonds. The results indicated that the diimidazolium based IL system showed promise as a biocompatible platform for the delivery of PTX. Diimidazolium ionic liquids, as low-toxicity solvents, are introduced into paclitaxel (PTX) dissolution systems for the first time, enhancing the dissolution of PTX in water and further promoting the design of biocompatible drug dissolution systems.