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 language | English |
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Pages (from-to) | 259-267 |
Number of pages | 8 |
Journal | Journal of Controlled Release |
Volume | 97 |
Issue number | 2 |
DOIs | |
Publication status | Published - 18 Jun 2004 |
Keywords
- Dendrimers
- Drug delivery
- Mechanism of transepithelial transport of dendrimer nanocarriers
- Transcellular and paracellular routes