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Soutenance de Thèse de Mr Norraseth Kaeokhamloed

Evaluation of lipid nanocapsules (LNCs) for oral absorption using new quantitative FRET technique

Lipid nanocapsules (LNCs) benefit from their ability to increase the oral bioavailability of the many encapsulated drugs, making them one of the promising oral nanomedicines. However, the oral absorption of the intact LNCs itself has not yet been well studied because of the lack of an appropriate tool. Hence, this thesis aims to characterize the oral absorption of intact LNCs in vitro and in vivo. LNCs with different sizes (50- and 85-nm) and surface modifications (none, DSPE-mPEG-2000, and stearylamine) were developed for the tests throughout the thesis. For the first part, the new in vitro coculture model of Caco-2 epithelium and HMEC-1 endothelium (Caco-2/HMEC-1 model) was developed to investigate the in vitro particle transport of LNCs across the epithelium-endothelium membranes. For the second part, the new quantitative (Förster resonance energy transfer) FRET technique was developed for quantitative analysis of intact LNCs in blood, liver, and feces. Then, the pharmacokinetics of intact LNCs was studied after IV administration using FRET. Finally, in vivo oral absorption of intact LNCs was studied in rats by evaluating 1) the oral bioavailability, 2) the biodistribution to hepatic portal vein and liver, and 3) the remaining intact LNC in the feces. The in vitro study found that intact LNCs had <1% transportation across the Caco-2/HMEC-1 model. The in vivo study found 0% in vivo oral bioavailability and 0% of intact LNCs is quantified in the hepatic portal vein, liver, and feces after 4 hours of oral gavage. The evidence suggests that intact LNCs may not be absorbed via the GI route.

Keywords: Lipid nanocapsules ; nanomedicines ; FRET ; oral absorption ; cell culture ; Caco-2

Directeur de Thèse: Dr Emilie ROGER

Co-directrice de thèse: Dr Samuel LEGEAY