期刊
PHARMACEUTICAL RESEARCH
卷 24, 期 11, 页码 2138-2145出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-007-9415-0
关键词
Caco-2 cells; intracellular trafficking; oral drug delivery; poly (amidoamine) dendrimers
资金
- NIGMS NIH HHS [F31-GM67278] Funding Source: Medline
To investigate the internalization and subcellular trafficking of fluorescently labeled poly (amidoamine) (PAMAM) dendrimers in intestinal cell monolayers. 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. 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. 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.
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