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

Nanoscale
Yen-Ling LinMohamed E H El-Sayed

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 org...Continue Reading

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Citations

Oct 11, 2011·Advanced Drug Delivery Reviews·S Sadekar, H Ghandehari
Jul 1, 2016·Tissue Barriers·Venkata K Yellepeddi, Hamidreza Ghandehari
May 6, 2015·Langmuir : the ACS Journal of Surfaces and Colloids·Mariam MoussaJérôme F L Duval
Aug 13, 2013·International Journal of Pharmaceutics·S SadekarH Ghandehari
May 4, 2018·Pharmaceutical Development and Technology·Mai Ahmed TawfikMagdy Ibrahim Mohamed
Aug 16, 2019·Expert Opinion on Drug Delivery·Venkata K Yellepeddi, Hamidreza Ghandehari

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