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Endocytosis and Interaction of Poly (Amidoamine) Dendrimers with Caco-2 Cells

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Abstract

Purpose

To investigate the internalization and subcellular trafficking of fluorescently labeled poly (amidoamine) (PAMAM) dendrimers in intestinal cell monolayers.

Materials and 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.

Conclusion

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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Abbreviations

FITC:

fluorescein isothiocyanate

G:

generation

HBSS:

hank’s balanced salt solution

PAMAM:

poly (amidoamine)

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Acknowledgements

The authors thank Dr. Richard Coleman and Maritza Patton for their assistance with the TEM studies. Financial support was provided by a pre-doctoral National Research Service Award from the National Institute of General Medical Sciences (F31-GM67278).

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Authors and Affiliations

  1. 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

    Kelly M. Kitchens, Amy B. Foraker, Rohit B. Kolhatkar, Peter W. Swaan & Hamidreza Ghandehari

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  1. Kelly M. Kitchens
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  2. Amy B. Foraker
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  3. Rohit B. Kolhatkar
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  4. Peter W. Swaan
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  5. Hamidreza Ghandehari
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Correspondence to Hamidreza Ghandehari.

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Kitchens, K.M., Foraker, A.B., Kolhatkar, R.B. et al. Endocytosis and Interaction of Poly (Amidoamine) Dendrimers with Caco-2 Cells. Pharm Res 24, 2138–2145 (2007). https://doi.org/10.1007/s11095-007-9415-0

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  • DOI: https://doi.org/10.1007/s11095-007-9415-0

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