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.

New Preparation Method Using Microwave, Kinetics, In Vitro Dissolution‐Diffusion, and Anti‐Inflammatory Study of Diclofenac‐ Proline Co–Crystal

“…These data confirm that the DPC had an improved dissolution profile from that of DA significantly in the intestinal pH. LP in physical mixture also pushed the dissolution rate due to its properties as a deep eutectic solvent in the solution, which has been established in many reports . However, DPC remain superior by increasing the DA dissolution rate compared to DA alone and physical mixture.…”

Polyphenols, Antioxidant, Antibacterial, and Biofilm Inhibitory Activities of Peel and Pulp of Citrus medica L., Citrus bergamia, and Citrus medica cv. Salò Cultivated in Southern Italy

“…Rutin is generally poorly absorbed; however, the use of appropriate natural solvents can improve its absorption and solubilization in the organism. This allows a greater recovery of the molecule, so as to open new frontiers in the field of nutraceuticals [29]. In other cases, some flavonoids were present only in the peel (e.g., quercetin in bergamot; catechin in cedar; quercetin and apigenin in cedar of Salò).…”

Development of a Method Based on Natural Deep Eutectic Solvents for Extraction of Flavonoids from Food Samples

“…These solvents have the following environmental and economic advantages: they are non-volatile, have a low toxicity, are biodegradable, sustainable, and inexpensive, and are made using simple preparation methods. They also show very good physicochemical properties: liquid state below 0°C, adjustable viscosity, a broad range of polarities, and ability to dissolve a wide range of compounds (Paiva et al 2014;Faggian et al 2006;Dai et al 2015). NADES therefore have good potential for the extraction of valuable secondary metabolites for use in the food and pharmaceutical industries.…”