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

• Published in: Green chemistry : an international journal and green chemistry resource : GC 2024-04, Vol.26 (7), p.413-423
• Main Authors: Hu, Yanhui, Yue, Hua, Huang, Shiqi, Song, Bingxi, Xing, Yuyuan, Liu, Minmin, Wang, Gongying, Diao, Yanyan, Zhang, Suojiang
• Format: Article
• Language: English
• Subjects: Biocompatibility; Cations; Cytotoxicity; Dissolution; Dissolving; Hydrogen bonding; Hydrogen bonds; Hydrophobicity; Ionic liquids; Liquids; Miscibility; Molecular chains; Paclitaxel; Solubility; Toxicity
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/d3gc04333a

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 [C 10 (MIM) 2 ][Br] 2 and water resulted in lower cytotoxicity at a certain concentration. Furthermore, [C 10 (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 [C 10 (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 [C 10 (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 [C 10 (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. 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.