title: Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal Tissue.
abstract: Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2 models innately lack mucous barriers, and rat isolated intestinal tissue has been shown to overestimate human permeability. This study is the first report of transport of PAMAM dendrimers across isolated human intestinal epithelium. It was observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM concentration do not have a statistically higher permeability compared to free FITC controls in isolated human jejunum and colonic tissues. Mannitol permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2 dendrimers. Significant histological changes in human colonic and jejunal tissues were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose limiting toxicity may occur at similar concentrations in vivo. The permeability through human isolated intestinal tissue in this study was compared to previous rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral drug delivery may be feasible, but it may be limited to highly potent drugs.
authors.affiliation: Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah , 36 South Wasatch Drive, Salt Lake City, Utah 84112, United States.|Department of Bioengineering, University of Utah , 36 South Wasatch Drive, Salt Lake City, Utah 84112, United States.
authors.forename: Dallin
authors.initials: D
authors.lastname: Hubbard
authors.affiliation: Juan Diego Catholic High School , 300 East 11800 South, Draper, Utah 84020, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Enda
authors.affiliation: Department of Chemistry, Brigham Young University Idaho , Rexburg, Idaho 83460, United States.
authors.forename: Tanner
authors.initials: T
authors.lastname: Bond
authors.affiliation: Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah , 36 South Wasatch Drive, Salt Lake City, Utah 84112, United States.|Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah , 36 South Wasatch Drive, Salt Lake City, Utah 84112, United States.
authors.forename: Seyyed Pouya Hadipour
authors.initials: SP
authors.lastname: Moghaddam
authors.affiliation: Department of Bioengineering, University of Utah , 36 South Wasatch Drive, Salt Lake City, Utah 84112, United States.
authors.forename: Josh
authors.initials: J
authors.lastname: Conarton
authors.affiliation: Department of Surgery, University of Utah , 30 North 1900 East, Salt Lake City, Utah 84132, United States.
authors.forename: Courtney
authors.initials: C
authors.lastname: Scaife
authors.affiliation: Department of Surgery, University of Utah , 30 North 1900 East, Salt Lake City, Utah 84132, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Volckmann
authors.affiliation: Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah , 36 South Wasatch Drive, Salt Lake City, Utah 84112, United States.|Department of Bioengineering, University of Utah , 36 South Wasatch Drive, Salt Lake City, Utah 84112, United States.|Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah , 36 South Wasatch Drive, Salt Lake City, Utah 84112, United States.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000493:pharmacokinetics*; D001692:Biological Transport; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D050091:Dendrimers / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000378:metabolism*; D008875:Middle Aged; D051381:Rats; D055815:Young Adult
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; C104700:PAMAM Starburst; D008353:Mannitol
keywords: Ussing chambers; human intestinal mucosae; oral drug delivery; poly(amido amine) dendrimers; toxicity; transport