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Issue 5, 2010
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Quantitative evaluation of the effect of poly(amidoamine) dendrimers on the porosity of epithelial monolayers

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Abstract

Poly(amidoamine) (PAMAM) dendrimers are a family of water-soluble polymers with a characteristic tree-like branching architecture and a large number of surface groups, which have been used to immobilize a variety of therapeutic molecules for targeted drug delivery. Earlier studies showed that small cationic PAMAM-NH2 and selected anionic PAMAM-COOH dendrimers permeate across in vitro models of the small intestinal epithelium by paracellular and transcellular transport mechanisms. The focus of this research is to mathematically calculate the effect of cationic, anionic, and neutral PAMAM dendrimers on the porosity of epithelial tight junctions as a function of dendrimers concentration, incubation time, generation number, and charge density. Results show that the increase in the concentration, incubation time and generation number of cationic G0–G2 PAMAM-NH2 and anionic G2.5 and G3.5 PAMAM-COOH dendrimers caused a corresponding increase in the porosity of Caco-2 cell monolayers. Neutral G2–G4 PAMAM-OH dendrimers had no effect on the porosity of intestinal cells. These results provide quantitative evidence that the observed increase in permeability of PAMAM dendrimers across Caco-2 cell monolayers is due to their effect on the organization of the tight junctions and the associated increase in membrane porosity. Furthermore, these results emphasize the potential of cationic PAMAM-NH2 and anionic PAMAM-COOH dendrimers to function as carriers for controlled oral drug delivery.

Graphical abstract: Quantitative evaluation of the effect of poly(amidoamine) dendrimers on the porosity of epithelial monolayers

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Article information


Submitted
11 Dec 2009
Accepted
23 Jan 2010
First published
17 Mar 2010

Nanoscale, 2010,2, 755-762
Article type
Paper

Quantitative evaluation of the effect of poly(amidoamine) dendrimers on the porosity of epithelial monolayers

Y. Lin, K. Khanafer and M. E. H. El-Sayed, Nanoscale, 2010, 2, 755
DOI: 10.1039/B9NR00407F

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