Transport of surface engineered polyamidoamine (PAMAM) dendrimers across IPEC-J2 cell monolayers

Drug Delivery
Dipak S PisalSrinath Palakurthi

Abstract

The aim of our study was to prepare arginine-and ornithine-conjugated Polyamidoamine (PAMAM) dendrimers and study their permeability across IPEC-J2 cell monolayers, a new intestinal cell line model for drug absorption studies. Arginine and ornithine were conjugated to the amine terminals of the PAMAM(G4) dendrimers by Fmoc synthesis. The apical-to-basolateral (AB) and basolateral-to-apical (BA) apparent permeability coefficients (P(app)) for the PAMAM dendrimers increased by conjugating the dendrimers with both of these polyamines. The enhancement in permeability was dependent on the dendrimer concentration and duration of incubation. Correlation between monolayer permeability and the decrease in transepithelial electrical resistance (TEER) with the PAMAM dendrimers and the polyamine-conjugated dendrimers suggests that paracellular transport is one of the mechanisms of transport across the epithelial cells. Cytotoxicity of these surface-modified dendrimers was evaluated in IPEC-J2 cells by MTT (methylthiazoletetrazolium) assay. Arginine-conjugated dendrimers were insignificantly more toxic than PAMAM dendrimer as well as ornithine-conjugated dendrimers. Though investigations on the possible involvement of other transport mechan...Continue Reading

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Citations

Jul 30, 2009·Expert Opinion on Drug Delivery·Venkata K YellepeddiSrinath Palakurthi
Nov 17, 2010·Critical Reviews in Toxicology·Jeffrey W CardBernadene A Magnuson
Oct 11, 2011·Advanced Drug Delivery Reviews·S Sadekar, H Ghandehari
Dec 3, 2014·Molecular Pharmaceutics·Balaji BharatwajSandro R P da Rocha
Jul 1, 2016·Tissue Barriers·Venkata K Yellepeddi, Hamidreza Ghandehari
Jan 1, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·U LodemannA Bondzio
Jul 1, 2016·Nanoscale Research Letters·Olena M PerepelytsinaLuciano Rosario Maria Vicari
Jan 17, 2019·Current Drug Targets·Jose Luis MarzoMassimiliano Pierobon
Jan 25, 2019·Current Drug Delivery·Nawzat D Al-JbourA K M Moshiul Alam

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