PURPOSE: To investigate systematically the effect of polyamidoamine (PAMAM) dendrimer size, charge, and concentration on uptake and transport across the adult rat intestine in vitro using the everted rat intestinal sac system. METHODS: Cationic PAMAM dendrimers (generations 3 and 4) and anionic PAMAM dendrimers (generations 2.5, 3.5, and 5.5) that were modified to include on average a single pendant amino group were radioiodinated using the Bolton and Hunter Reagent. 125I-Labelled dendrimers were incubated with everted sacs in vitro and the transfer of radioactivity into the tissue and serosal fluid was followed with time. RESULTS: The serosal transfer rates seen for all anionic generations were extremely high with Endocytic Indices (EI) in the range 3.4-4.4 microL/mg protein/h. The concentration-dependence of serosal transfer was linear over the dendrimer concentration range 10-100 microg/mL. For 125I-labelled generation 5.5 the rate of tissue uptake was higher (EI = 2.48+/-0.51 microL/mg protein/h) than seen for 125I-labelled generations 2.5 and 3.5 (0.6-0.7 microL/mg protein/h) (p < 0.05). The 125I-labelled cationic PAMAM dendrimers (generations 3 and 4) displayed a tissue uptake (EI = 3.3-4.8 microL/mg protein/h) which was higher (p < 0.05) than the rate of serosal transfer (EI = 2.3-2.7 microL/mg protein/h), probably due to nonspecific adsorption of cationic dendrimer to the mucosal surface. CONCLUSIONS: As the anionic PAMAM dendrimers displayed serosal transfer rates that were faster than observed for other synthetic and natural macromolecules (including tomato lectin) studied in the everted sac system, these interesting nanoscale structures may have potential for further development as oral drug delivery systems.
PURPOSE: To investigate systematically the effect of polyamidoamine (PAMAM) dendrimer size, charge, and concentration on uptake and transport across the adult rat intestine in vitro using the everted rat intestinal sac system. METHODS: Cationic PAMAM dendrimers (generations 3 and 4) and anionic PAMAM dendrimers (generations 2.5, 3.5, and 5.5) that were modified to include on average a single pendant amino group were radioiodinated using the Bolton and Hunter Reagent. 125I-Labelled dendrimers were incubated with everted sacs in vitro and the transfer of radioactivity into the tissue and serosal fluid was followed with time. RESULTS: The serosal transfer rates seen for all anionic generations were extremely high with Endocytic Indices (EI) in the range 3.4-4.4 microL/mg protein/h. The concentration-dependence of serosal transfer was linear over the dendrimer concentration range 10-100 microg/mL. For 125I-labelled generation 5.5 the rate of tissue uptake was higher (EI = 2.48+/-0.51 microL/mg protein/h) than seen for 125I-labelled generations 2.5 and 3.5 (0.6-0.7 microL/mg protein/h) (p < 0.05). The 125I-labelled cationic PAMAM dendrimers (generations 3 and 4) displayed a tissue uptake (EI = 3.3-4.8 microL/mg protein/h) which was higher (p < 0.05) than the rate of serosal transfer (EI = 2.3-2.7 microL/mg protein/h), probably due to nonspecific adsorption of cationic dendrimer to the mucosal surface. CONCLUSIONS: As the anionic PAMAM dendrimers displayed serosal transfer rates that were faster than observed for other synthetic and natural macromolecules (including tomato lectin) studied in the everted sac system, these interesting nanoscale structures may have potential for further development as oral drug delivery systems.
Authors: N Malik; R Wiwattanapatapee; R Klopsch; K Lorenz; H Frey; J W Weener; E W Meijer; W Paulus; R Duncan Journal: J Control Release Date: 2000-03-01 Impact factor: 9.776
Authors: Jason H Sakamoto; Anne L van de Ven; Biana Godin; Elvin Blanco; Rita E Serda; Alessandro Grattoni; Arturas Ziemys; Ali Bouamrani; Tony Hu; Shivakumar I Ranganathan; Enrica De Rosa; Jonathan O Martinez; Christine A Smid; Rachel M Buchanan; Sei-Young Lee; Srimeenakshi Srinivasan; Matthew Landry; Anne Meyn; Ennio Tasciotti; Xuewu Liu; Paolo Decuzzi; Mauro Ferrari Journal: Pharmacol Res Date: 2010-01-05 Impact factor: 7.658
Authors: Andrzej Myc; Jolanta Kukowska-Latallo; Peter Cao; Ben Swanson; Julianna Battista; Thomas Dunham; James R Baker Journal: Anticancer Drugs Date: 2010-02 Impact factor: 2.248