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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
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Flavonoid metabolites transport across a human BBB model
Ana Faria1, Manuela Meireles, Iva Fernandes
1Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; Chemistry Investigation Centre (CIQ), Department of Chemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal; Faculty of Nutrition and Food Sciences, University of Porto, 4200-465 Porto, Portugal.
Food Chemistry
|December 4, 2013
Summary
Flavonoids and their metabolites effectively cross the blood-brain barrier (BBB) model. Metabolites generally showed higher transport efficiency than native flavonoids, suggesting potential for brain-targeted delivery.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Flavonoids are plant compounds with potential therapeutic benefits.
- Understanding their ability to cross the blood-brain barrier (BBB) is crucial for neurological drug development.
- The transport mechanisms of various flavonoid classes and their metabolites across the BBB remain incompletely understood.
Purpose of the Study:
- To investigate the transmembrane transport of diverse flavonoids (flavan-3-ols, anthocyanins, flavonols) and their metabolites across a human cerebral microvascular endothelial cell (hCMEC/D3) model of the BBB.
- To explore the metabolism and transport modulation of these compounds to elucidate underlying mechanisms.
- To determine the efficiency and kinetics of flavonoid and metabolite passage across the BBB model.
Main Methods:
- Utilized hCMEC/D3 cells as an in vitro blood-brain barrier (BBB) model.
- Employed High-Performance Liquid Chromatography with Diode-Array Detection and Mass Spectrometry (HPLC-DAD/MS) to quantify transported compounds.
- Monitored transport in basolateral media at 1, 3, and 18 hours, assessing time-dependent kinetics and effects of modulators.
Main Results:
- All tested flavonoids and their metabolites demonstrated time-dependent transport across the hCMEC/D3 cell model.
- Flavonoid metabolites exhibited generally higher transport efficiency compared to their parent compounds.
- Anthocyanin transport correlated with lipophilicity, while quercetin transport was modulated by phosphatase inhibitors, indicating phosphorylation involvement.
Conclusions:
- Flavonoids and their metabolites possess the capability to permeate the blood-brain barrier (BBB).
- Metabolites may offer improved BBB penetration compared to native flavonoids.
- The transport mechanisms involve factors like lipophilicity and potentially phosphorylation/dephosphorylation processes, suggesting avenues for optimizing brain delivery.
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