title: Transepithelial transport of PAMAM dendrimers across isolated rat jejunal mucosae in ussing chambers.
abstract: Oral delivery remains a challenge for poorly permeable hydrophilic macromolecules. Poly(amido amine) (PAMAM) dendrimers have shown potential for their possible oral delivery. Transepithelial transport of carboxyl-terminated G3.5 and amine-terminated G4 PAMAM dendrimers was assessed using isolated rat jejunal mucosae mounted in Ussing chambers. The 1 mM FITC-labeled dendrimers were added to the apical side of mucosae. Apparent permeability coefficients (Papp) from the apical to the basolateral side were significantly increased for FITC when conjugated to G3.5 PAMAM dendrimer compared to FITC alone. Minimal signs of toxicity were observed when mucosae were exposed to both dendrimers with respect to transepithelial electrical resistance changes, carbachol-induced short circuit current stimulation, and histological changes. [(14)C]-mannitol fluxes were not altered in the presence of 1 mM dendrimers, suggesting that the paracellular pathway was not affected at this concentration in this model. These results give insight into the mechanism of PAMAM dendrimer transepithelial rat jejunal transport, as well as toxicological considerations important for oral drug delivery.
authors.affiliation: Utah Center for Nanomedicine, Nano Institute of Utah, ‡Department of Bioengineering, and §Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah , 36 S. Wasatch Blvd., Salt Lake City, Utah 84112, United States.
authors.forename: Dallin
authors.initials: D
authors.lastname: Hubbard
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
authors.forename: David J
authors.initials: DJ
authors.lastname: Brayden
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007583:Jejunum / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst