Influence of PEGylation of Vitamin-K-Loaded Mixed Micelles on the Uptake by and Transport through Caco‑2 Cells

The aim of the study is to investigate the uptake by and transport through Caco-2 cells of two mixed micelle formulations (based on egg phosphatidylcholine and glycocholic acid) of vitamin K, i.e., with and without DSPE-PEG2000. The uptake of vitamin K and fluorescently labeled mixed micelles with a...

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Bibliographic Details
Published in:Molecular pharmaceutics 2018-09, Vol.15 (9), p.3786-3795
Main Authors: Sun, Feilong, Adrian, Max, Beztsinna, Nataliia, van den Dikkenberg, Joep B, Maas-Bakker, Roel F, van Hasselt, Peter M, van Steenbergen, Mies J, Su, Xiangjie, Kapitein, Lukas C, Hennink, Wim E, van Nostrum, Cornelus F
Format: Article
Language:English
Subjects:
Biological Transport - drug effects
Caco-2 Cells
Humans
Micelles
Phosphatidylethanolamines - chemistry
Polyethylene Glycols - chemistry
Scavenger Receptors, Class B - metabolism
Vitamin K - chemistry
Vitamin K - pharmacology
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Summary:The aim of the study is to investigate the uptake by and transport through Caco-2 cells of two mixed micelle formulations (based on egg phosphatidylcholine and glycocholic acid) of vitamin K, i.e., with and without DSPE-PEG2000. The uptake of vitamin K and fluorescently labeled mixed micelles with and without PEG coating showed similar kinetics and their uptake ratio remained constant over time. Together with the fact that an inhibitor of scavenger receptor B1 (BLT-1) decreased cellular uptake of vitamin K by ∼80% compared to the uptake in the absence of this inhibitor, we conclude that both types of micelles loaded with vitamin K can be taken up intactly by Caco-2 cells via this scavenger receptor. The amount of vitamin K in chylomicrons fraction from Caco-2 cell monolayers further indicates that mixed micelles (with or without PEGylation) are likely packed into chylomicrons after internalization by Caco-2 cells. Uptake of vitamin K from PEGylated mixed micelles increased four- to five-fold at simulated gastrointestinal conditions. In conclusion, PEGylated mixed micelles are stable upon exposure to simulated gastric conditions, and as a result, they do show overall a higher cellular uptake efficiency of vitamin K as compared to mixed micelles without PEG coating.
ISSN:1543-8384
1543-8392
DOI:10.1021/acs.molpharmaceut.8b00258