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Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model

Item Type:Article
Title:Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model
Creators Name:Orthmann, A. and Zeisig, R. and Koklic, T. and Sentjurc, M. and Wiesner, B. and Lemm, M. and Fichtner, I.
Abstract:The aim of this study was to investigate the effect of liposomal membrane properties on cellular uptake and transcytosis across a tight Madin-Darby canine kidney (MDCK) cell barrier in vitro. More than 25 small vesicles were prepared by lipid film hydration/extrusion to generate small unilamellar vesicles. The fluorescence marker calcein was encapsulated to mimic hydrophilic drug transport. Marker uptake by MDCK cells seems to be mediated by different mechanisms for the liposomes used. It was mainly depending on membrane fluidity and vesicle charge. Liposomes L2 with a positive charge (325 +/- 3 pmol/well) and vesicles L3 containing the helper lipid dioleylphosphatidylethanolamine (DOPE) in their membrane (216 +/- 42 pmol/well) were taken up to the most. Selected liposomes were tested for their transcytotic transport across a MDCK monolayer. Liposomes L4 containing equimolar DOPE and octadecyl-1,1-dimethylpiperidin-1-ium-4-yl phosphate (OPP) were the most efficient vesicles for transcellular transport resulting in 808 +/- 30 pmol calcein/cm(2) in the basal medium (28.1% of total liposomal marker added). Transcytosis was positively correlated with membrane fluidity in the outer part of the bilayer, as electron paramagnetic resonance measurements revealed. We expect that an increase in membrane fluidity of vesicles should also improve the restricted transport of hydrophilic drugs across the blood-brain barrier.
Keywords:Liposomes, Helper Lipid, Transcytosis, Cellular Uptake, Electron Paramagnetic Resonance, MDCK Cells, Animals, Dogs
Source:Journal of Pharmaceutical Sciences
ISSN:0022-3549
Publisher:Wiley-Blackwell (U.S.A.)
Volume:99
Number:5
Page Range:2423-2433
Date:May 2010
Official Publication:https://doi.org/10.1002/jps.22001
PubMed:View item in PubMed

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