Transport of dendrimer nanocarriers through epithelial cells via the transcellular route

Rachaneekorn Jevprasesphant, Jeffrey Penny, David Attwood, Antony D'Emanuele

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The mechanism of transport of G3 PAMAM and surface-modified (with lauroyl chains) G3 PAMAM dendrimer nanocarriers across Caco-2 cell monolayers has been investigated. Flow-cytometry studies following quenching of extracellular fluorescence demonstrated the cellular internalisation of dendrimers. Optical sectioning of cells incubated with fluorescein isothiocyanate (FITC)-conjugated dendrimer and lauroyl-dendrimer using confocal laser scanning microscopy revealed colocalisation of a marker for cell nuclei (4′,6-diamidino-2- phenylindole, DAPI) and FITC fluorescence, also suggesting cellular internalisation of dendrimers. Transmission electron microscopic analyses of cells incubated with gold-labelled G3 PAMAM dendrimers confirmed endocytosis-mediated cellular internalisation when dendrimers were applied to the apical domain of Caco-2 cells. These findings are in agreement with our previous studies using Caco-2 cell monolayers that showed a significant decrease of dendrimer uptake in the presence of colchicine (endocytosis inhibitor) and when temperature was reduced from 37 to 4°C. © 2004 Elsevier B.V. All rights reserved.
    Original languageEnglish
    Pages (from-to)259-267
    Number of pages8
    JournalJournal of Controlled Release
    Volume97
    Issue number2
    DOIs
    Publication statusPublished - 18 Jun 2004

    Keywords

    • Dendrimers
    • Drug delivery
    • Mechanism of transepithelial transport of dendrimer nanocarriers
    • Transcellular and paracellular routes

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