title: 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.
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.
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy. marta.faggian@studenti.unipd.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Faggian
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy. stefania_sut@hotmail.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sut
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy. bperissutti@units.it.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Perissutti
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy. valeria.baldan.4@studenti.unipd.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Baldan
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, SI-1000 Ljubljana, Slovenia. Iztok.Grabnar@ffa.uni-lj.si.
authors.forename: Iztok
authors.initials: I
authors.lastname: Grabnar
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy. stefano.dallacqua@unipd.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Dall'Acqua
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001688:Biological Products / Q000737:chemistry*; D019587:Dietary Supplements / Q000032:analysis; D005998:Glycine / Q000737:chemistry*; D008297:Male; D051379:Mice; D010949:Plasma / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D051381:Rats; D012431:Rutin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D001688:Biological Products; D012997:Solvents; D014867:Water; D012431:Rutin; D011392:Proline; D005998:Glycine
keywords: HPLC-MS; NADES; pharmacokinetics; rutin