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Article Dans Une Revue Journal of Controlled Release Année : 2022

Pharmacokinetics of intact lipid nanocapsules using new quantitative FRET technique

Adélie Mellinger
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Jérôme Bejaud
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Samuel Legeay
Emilie Roger

Résumé

The present study investigated the pharmacokinetics of intact lipid nanocapsules (LNCs) after intravenous administration in rats. Six different Förster resonance energy transfer LNCs (FRET-LNCs) have been studied with 2 sizes (50 and 85 nm) and 3 coating types (none, DSPE-mPEG 2000 or stearylamine). A FRET-LNCs blood extraction method was developed to retain an accurate FRET signal. Intact FRET-LNCs were specifically quantified through combination of FRET signal and Nano Tracker Analysis. Pharmacokinetic data were first described by non-compartmental analysis, then used to develop a population pharmacokinetic model. The pharmacokinetic elimination of FRET-LNCs was non-linear and dependent on size and surface modification, while the distribution was dependent on size. The LNCs 85 nm volume of distribution was lower than LNCs 50 nm. As expected, LNCs 85 nm with PEG coating displayed a lower clearance than other formulations. Surprisingly, this study highlighted a faster elimination of LNCs 50 nm with PEG compared to other formulations which could be explained by instability in blood. This first pharmacokinetic model of intact LNCs allowed a thorough understanding of the influence of size and coating on pharmacokinetic properties and paves the way for future mechanistic modeling approaches to predict the fate of LNCs in vivo.
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Dates et versions

hal-02341627 , version 1 (31-10-2019)

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Vincent Lebreton, Norraseth Kaeokhamloed, Anastasiia Vasylaki, Gregory Hilairet, Adélie Mellinger, et al.. Pharmacokinetics of intact lipid nanocapsules using new quantitative FRET technique. Journal of Controlled Release, 2022, 351, pp.681-691. ⟨10.1016/j.jconrel.2017.03.005⟩. ⟨hal-02341627⟩
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