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

Abstract

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, π–π stacking, CH–π interactions, and hydrogen bonds. The results indicated that the diimidazolium based IL system showed promise as a biocompatible platform for the delivery of PTX.