Green and controllable fabrication of nanocrystals from ionic liquids

Nanocrystals are of great value in delivering poorly soluble drugs as a technique enables enhanced dissolution and bioavailability. The bottom-up technique allows better control of particle properties. However, the commonly used organic solvents are hazardous to environment and operators, and always lead to large particle size and wide size distribution due to failure on controlling the nucleation and crystal growth. The situation is exacerbated in scale-up production. Therefore, in the proof-of-concept study, we evaluated the feasibility of green and controllable fabrication of drug nanocrystals by using biocompatible ionic liquids (ILs) as solvents. Choline based ILs (Ch-ILs) were synthesized via metathesis reactions. Pure paclitaxel nanocrystals of high quality were obtained from Ch-ILs with surface tension higher than 42 mN/m. The sizes were below 250 nm, while the polydispersity indexes were lower than 0.25. Compared with ethanol, choline lactate is superior in controlling the size of the nanocrystals in scale-up production, where the drug concentration was increased by 6 times. The underlying mechanism may be due to the high viscosity and low surface tension of the ILs, which are supposed to benefit homogeneous and burst nucleation. Ch-ILs can be recycled from the process and recovery rate reached 91.1%. Moreover, the applicability of the green technique was validated in a wider range of model drugs and Ch-ILs. In conclusion, ILs are potent solvents in bottom-up technique for green and controllable fabrication of nanocrystals. (C) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.