Poor drug solubility or loading, inflexible drug release profiles, and poor storage stability are some of the most difficult issues to surpass in the production of efficient and safe controlled delivery systems. So, due to their suitable properties, ionic liquids (ILs) may be used as new functional materials to overcome these drawbacks. ILs are organic salts, which may be introduced in different types of drug delivery systems.

Herein, 5 ILs — two imidazole-based and three choline-aminoacid —were synthesized and their applicability as functional materials in drug delivery systems, at non-toxic concentrations, was evaluated.

Firstly, their cytotoxicity in human keratinocytes (HaCaT) was evaluated, and considering these results, it was developed the controlled drug delivery systems in the presence and absence of the ILs. Each IL was incorporated at the upper concentration of these salts allowing the maintenance of cell viability. Lipidic implants and transfersomes without and with IL (TransfersomILs) were the chosen lipid-based controlled delivery systems to investigate the impact of adding ILs. In these studies, rutin was used as a model drug with poor aqueous solubility.

Our results showed that the ILs promoted a significantly higher drug loading, with the choline-based ILs displaying better results when compared with the imidazole-based ILs. The incorporation of ILs showed that they seem to modulate the release profile of the drug from the lipidic implants. Regarding TransfersomILs, they demonstrated a higher association efficiency with a higher total amount of drug release, and better colloidal and storage stability when compared with the transfersomes without ILs.

In conclusion, the incorporation of ILs, at non-toxic concentrations, allowed the development of more efficient controlled delivery systems, showing that ILs may be multifunctional and valuable materials to boost the performance of delivery systems.