Study on the properties and in vitro transdermal delivery and cytotoxicity of drug-active ionic liquids with matrine as the cation†

Combining ionic liquids with active pharmaceutical ingredients (API-ILs) is an ideal strategy to improve the biopharmaceutical properties of APIs while preserving their efficacy. The appropriate selection of anions and cations for the formation of ILs eliminates the problems of solid drugs and retains the core ideal characteristics of the ionic liquid material state. In this study, API-ILs were prepared using matrine (Mat) as a cation and non-steroidal anti-inflammatory drugs (NSAIDs) as anions to improve the undesirable properties of NSAIDs and prepare API-ILs with dual functions. Mass spectrometry showed that the drug molecules exist as anions and cations in the ionic liquid. Infrared, nuclear magnetic and computer simulations demonstrated that Mat-NSAID interactions were mediated by hydrogen bonds, ionic bonds and van der Waals forces. Evaluation of physicochemical properties shows that ILs exhibited better solubility, where the solubilities of loxoprofen and diclofenac were 287 and 220 times higher, respectively, than that of the bulk drug. In addition, cytotoxicity tests were performed prior to in vitro skin penetration studies. The accumulation of diclofenac and loxoprofen ionic liquids in the skin was better than that of the corresponding APIs. These results suggest that the utilization of ionic liquids is a simple and effective strategy to improve the undesirable properties of drugs, and the effective selection of cations and anions is essential to regulate the pharmaceutical properties of drugs.