Anti-inflammatory choline based ionic liquids: Insights into their lipophilicity, solubility and toxicity parameters

作者：Azevedo Ana M O; Costa Susana P F; Dias Ana F V; Marques Alexandre H O; Pinto Paula C A G; Bica Katharina; Ressmann Anna K; Passos Marieta L C; Araujo Andre R T S; Reis Salette; Saraiva M Lucia M F S^*

来源：Journal of Molecular Liquids, 2017, 232: 20-26.

DOI：10.1016/j.molliq.2017.02.027

• Non-steroidal anti-inflammatory drugs
• Ionic liquids
• Partition coefficient
• Shake flask method
• Cytochrome c oxidase

The impact on in vivo efficacy and safety of two novel ionic liquids based on the association of choline with non steroidal anti-inflammatory drugs, ketoprofen and naproxen forming IL-APIs, was evaluated. Their lipophilicity, solubility and toxicity were assessed aiming the illustration of the pharmaceutical profile and potential toxic impact.
Partition coefficient was determined using micelles of hexadecylphosphocholine and UV-Vis derivative spectroscopy. Additionally, solubility in phosphate buffer pH 7.4 was measured using a modified shake flask method and UV-Vis spectroscopy as detection technique. Ultimately, toxicity was considered resorting to a fully automated cytochrome c oxidase assay based on microfluidics. The obtained results demonstrated that the IL-APIs' drug format has the ability to interact with biological membranes and also improves solubility up to 58 times. Moreover, it was evidenced that, although being a nutrient, choline influences the IL-APIs' toxicity. The studied anti-inflammatory IL-APIs exhibited promising properties regarding their incorporation in pharmaceutical formulations.

• 出版日期2017-4