title: Transport mechanism(s) of poly (amidoamine) dendrimers across Caco-2 cell monolayers.
abstract: The objective of this research was to investigate the mechanism(s) of transport of generation 2 (G2) poly (amidoamine) dendrimers across Caco-2 cell monolayers. The contribution of an energy-dependent process such as adsorptive endocytosis was investigated by determining G2 permeability at 4 and 37 degrees C. The contribution of P-gp efflux to transport was examined by determining the apical to basolateral (AB) and basolateral to apical (BA) permeability of 14C-paclitaxel in presence of G2, and by determining AB and BA permeability of G2 in presence of paclitaxel. The permeability of G2 and 14C-mannitol was investigated in the presence of palmitoyl carnitine to determine the contribution of the paracellular pathway. Permeability of G2 at 4 degrees C was significantly (P<0.05) lower than that observed at 37 degrees C. AB and BA permeability of 14C-paclitaxel did not change in the presence of G2. AB and BA permeability of G2 did not change in the presence of paclitaxel. The permeability of G2 and 14C-mannitol increased significantly (P<0.05) in the presence of palmitoyl carnitine, and in addition, 14C-mannitol permeability was increased in presence of G2. The permeability of G2 across Caco-2 cell monolayers appears to involve a combination of paracellular transport and an energy-dependent process, possibly adsorptive endocytosis. G2 dendrimers do not appear to be substrates for the P-gp efflux system.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 N. Pine Street, Baltimore, MD 21201, USA.
authors.forename: M
authors.initials: M
authors.lastname: El-Sayed
authors.forename: C A
authors.initials: CA
authors.lastname: Rhodes
authors.forename: M
authors.initials: M
authors.lastname: Ginski
authors.forename: H
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D001672:Biocompatible Materials / Q000493:pharmacokinetics*; D001692:Biological Transport; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D050091:Dendrimers; D004337:Drug Carriers / Q000493:pharmacokinetics; D006801:Humans; D011073:Polyamines / Q000493:pharmacokinetics*
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D011073:Polyamines