Endocytosis and interaction of poly (amidoamine) dendrimers with Caco-2 cells.
OBJECTIVE
To investigate the internalization and subcellular trafficking of fluorescently labeled poly (amidoamine) (PAMAM) dendrimers in intestinal cell monolayers.


METHODS
PAMAM dendrimers with positive or negative surface charge were conjugated to fluorescein isothiocyanate (FITC) and visualized for colocalization with endocytosis markers using confocal microscopy. Effect of concentration, generation and charge on the morphology of microvilli was observed using transmission electron microscopy.


RESULTS
Both cationic and anionic PAMAM dendrimers internalized within 20 min, and differentially colocalized with endocytosis markers clathrin, EEA-1, and LAMP-1. Transmission electron microscopy analysis showed a concentration-, generation- and surface charge-dependent effect on microvilli morphology.


CONCLUSIONS
These studies provide visual evidence that endocytic mechanism(s) contribute to the internalization and subcellular trafficking of PAMAM dendrimers across the intestinal cells, and that appropriate selection of PAMAM dendrimers based on surface charge, concentration and generation number allows the application of these polymers for oral drug delivery.
Kitchens
Kelly M
KM
Center for Nanomedicine and Cellular Delivery, Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, HSFII-Room 625, Baltimore, Maryland 21201-1075, USA.
Foraker
Amy B
AB
Kolhatkar
Rohit B
RB
Swaan
Peter W
PW
Ghandehari
Hamidreza
H
D018938:Caco-2 Cells; D050091:Dendrimers; D017097:Electric Impedance; D004705:Endocytosis; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000032:analysis; D011073:Polyamines / Q000493:pharmacokinetics*; D052118:Lysosomal-Associated Membrane Protein 1
D050091:Dendrimers; D051907:Lysosomal Membrane Proteins; D011073:Polyamines; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C104700:PAMAM Starburst
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