Trans-ε-Viniferin Encapsulation in Multi-Lamellar Liposomes: Consequences on Pharmacokinetic Parameters, Biodistribution and Glucuronide Formation in Rats.

Pauline Beaumont,Pierre-Louis Teissedre,Claude Atgié,Tristan Richard,Chrystel Faure,Arnaud Courtois,Stéphanie Krisa,Axel Marchal,Michael Jourdes

doi:10.3390/nu13124212

Abstract

Trans-ε-viniferin (εVin) is a resveratrol dimer exhibiting promising biological activities for human health. Its bioavailability being low, the development of encapsulation methods would be used to overcome this issue. The aim of this study was to measure the consequences of the encapsulation of εVin in multilamellar liposomes on its pharmacokinetic parameters, metabolism and tissue distribution in rats. After oral administration of εVin (20 mg/kg body weight), either as free or encapsulated forms, plasmas were sequentially collected (from 0 to 4 h) as well as liver, kidneys and adipose tissues (4 h after administration) and analyzed by LC-HRMS. The glucuronide metabolites (εVG) were also produced by hemisynthesis for their quantification in plasma and tissues. The encapsulation process did not significantly modify the pharmacokinetic parameters of εVin itself. However, a significant increase of the T1/2 was noticed for εVG after administration of the encapsulated form as compared to the free form. An accumulation of εVin and εVG in adipose tissues was noticed, and interestingly a significant increase of the latter in the mesenteric one after administration of the encapsulated form was highlighted. Since adipose tissues could represent storage depots, and encapsulation allows for prolonging the exposure time of glucuronide metabolites in the organism, this could be of interest to promote their potential biological activities.

Highlights

Trans-ε-viniferin is a resveratrol dehydrodimer belonging to the stilbene’s family
This study aimed to investigate the consequences of εVin encapsulation in onion-type multi-lamellar liposomes (MLLs) on its pharmacokinetic parameters and tissular distribution after oral administration in rats
Limit of Quantification (LOQ) were defined as the lowest concentrations for which trueness and precision (RSD) were less than 15%

Summary

Introduction

Trans-ε-viniferin (εVin) is a resveratrol dehydrodimer belonging to the stilbene’s family. Stilbenes are phytoalexins present in several edible plant families [1]. The main source of these compounds in European food is grapes [2] and their derivative products such as grapes juice or wine, and peanuts and red fruits [3,4]. The average daily consumption of stilbenes differs according to several criteria but is estimated at 0.5 mg/person/day according to a Spanish study, and 0.3 mg/person/day according to a Chinese one [3,5,6]. Numerous studies on the biological properties of εVin, a dimer present in red wines [7] in the wood of Vitis vinifera (up to 7.7 g/kg dry weight, more abundant than resveratrol [8]), have shown that this molecule could have some benefits for human health

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