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. 2016 Nov 14;21(11):1531.
doi: 10.3390/molecules21111531.

Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals

Marta Faggian  1 , Stefania Sut  2 , Beatrice Perissutti  3 , Valeria Baldan  4 , Iztok Grabnar  5 , Stefano Dall'Acqua  6
Affiliations

Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals

Marta Faggian et al. Molecules. .

Abstract

There is a need for innovation in plant-derived pharmaceuticals, food supplements and nutraceutical products regarding the use of more eco-sustainable solvents for their extraction. Furthermore, the poor oral bioavailability of several phytochemicals with health promoting effects stimulates the research in the field of pharmaceutical formulations. Natural Deep Eutectic Solvents (NADES) are formed by natural compounds, and can be considered as future solvents being especially useful for the preparation of nutraceuticals and food-grade extracts. In this paper various NADES were prepared using sugars, aminoacids and organic acids. Rutin (quercetin-3-O-α-l-rhamnopyranosyl-(1→6))-β-d-glucopyranose) was used as a model compound to study NADES. Moreover, the effect of various eutectic mixtures on rutin's water solubility was studied. Proline/glutamic acid (2:1) and proline/choline chloride (1:1) mixtures have a solubility comparable to ethanol. The proline/glutamic acid (2:1) eutectic containing rutin was used in a pharmacokinetic study in Balb/c mice while bioavailability was compared to oral dosing of water suspension. Plasmatic levels of rutin were measured by HPLC-MS/MS showing increased levels and longer period of rutin permanence in plasma of NADES treated animals. This paper reports the possible use of non-toxic NADES for pharmaceutical and nutraceutical preparations.

Keywords: HPLC-MS; NADES; pharmacokinetics; rutin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Solubility ratio of rutin (solvent/water) in each prepared NADES. The solubility in all solvents were significantly different from solubility in water (p-values < 0.05).
Figure 2
Figure 2
HPLC-MS/MS chromatograms corresponding to transitions 609 > 301 for rutin and 481 > 124 for ISTD (silimarin) of blank plasma (traces red and green for rutin and ISTD respectively) and plasma spiked with rutin and ISTD (traces yellow and blue for rutin and ISTD respectively).
Figure 3
Figure 3
Time course (mean ± SD) of plasma concentration time course of rutin in Balb/c mice following oral administration of 10 mg as proline/glutamic NADES or suspension in water.
See this image and copyright information in PMC

References

    1. Joana Gil-Chávez G., Villa J.A., Fernando Ayala-Zavala J., Basilio Heredia J., Sepulveda D., Yahia E.M., González-Aguilar G.A. Technologies for Extraction and Production of Bioactive Compounds to be used as Nutraceuticals and Food Ingredients: An Overview. Compr. Rev. Food Sci. Food Saf. 2013;12:5–23. doi: 10.1111/1541-4337.12005. - DOI
    1. Chemat F., Vian M.A., Cravotto G. Green Extraction of Natural Products: Concept and Principles. Int. J. Mol. Sci. 2012;13:8615–8627. doi: 10.3390/ijms13078615. - DOI - PMC - PubMed
    1. Espín J.C., García-Conesa M.T., Tomás-Barberán F.A. Nutraceuticals: Facts and Fiction. Phytochemistry. 2007;68:2986–3008. doi: 10.1016/j.phytochem.2007.09.014. - DOI - PubMed
    1. Sut S., Baldan V., Faggian M., Peron G., Dall’Acqua S. Nutraceuticals, a New Challenge for Medicinal Chemistry. Curr. Med. Chem. 2016;23:1–26. doi: 10.2174/0929867323666160615104837. - DOI - PubMed
    1. Paiva A., Craveiro R., Aroso I., Martins M., Reis R.L., Duarte A.R.C. Natural Deep Eutectic Solvents—Solvents for the 21st Century. ACS Sustain. Chem. Eng. 2014;2:1063–1071. doi: 10.1021/sc500096j. - DOI