Transport mechanism(s) of poly (amidoamine) dendrimers across Caco-2 cell monolayers

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 degreesC. The contribution of P-gp efflux to transport was examined by determining the apical to basolateral (AB) and basolateral to apical (BA) permeability of C-14-paclitaxel in presence of G2, and by determining AB and BA permeability of G2 in presence of paclitaxel. The permeability of G2 and C-14-mannitol was investigated in the presence of palmitoyl carnitine to determine the contribution of the paracellular pathway. Permeability of G2 at 4 degreesC was significantly (P < 0.05) lower than that observed at 37 degreesC. AB and BA permeability of C-14-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 C-14-mannitol increased significantly (P < 0.05) in the presence of palmitoyl carnitine, and in addition, C-14-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. (C) 2003 Elsevier B.V. All rights reserved.