Anti-inflammatory choline based ionic liquids: Insights into their lipophilicity, solubility and toxicity parameters
2017
Abstract 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.
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