Choline ester based ionic liquid: A multi-functional system to enhance nucleic acid stability, drug solubilization and cell penetration

Ionic liquids (ILs) are emerging systems with applications in varying areas of biomedical research. This study aims at developing a biocompatible, dual function choline ester-based IL with chloride as anion ([Ch] IL) for stabilizing nucleic acids (DNA) and enhancing cellular uptake of drugs. The ability of IL to complex with DNA was characterized using electrophoresis, dye displacement and UV absorbance. The effect of pH on complex stability and protection of DNA from nuclease were also studied. Even though [Ch] IL had positive zeta potential and showed effective complex formation, at physiological pH the zeta potential of the complex decreased and became negative, thereby, destabilizing the complex. To address this, citric acid (CA) was added to [Ch] IL which facilitated strong complexation. Further, DNA could be retrieved from these complexes without compromising its purity and integrity. Additionally, [Ch] IL was found to improve the cellular uptake of doxorubicin by improving its solubility in water. Thus, we demonstrate that the [Ch] IL developed here can enhance nucleic acid stability, drug solubilization and cell penetration. Our results show that the developed [Ch] IL can be used for long term storage of nucleic acids as well as for enhancing permeation of drugs in vivo.