Anionic PAMAM dendrimers rapidly cross adult rat intestine<I> in vitro</I> : A potential oral delivery system?

Anionic PAMAM dendrimers rapidly cross adult rat intestine in vitro : A potential oral delivery system?

Ruedeekorn Wiwattanapatapee, Asst. Prof., D. of Pharmaceutical Tech., F. of Pharmaceutical Sci, PSU.
Begona carreno-Gomez, Centre for Polymer Therapeutics, The School of Pharmacy, U. of London, UK.
Navid Malik, Centre for Polymer Therapeutics, The School of Pharmacy, U. of London, UK.
Ruth Duncan, Centre for Polymer Therapeutics, The School of Pharmacy, U. of London, UK.
Corresponding e-mail : wruedeek@ratree.psu.ac.th

Published : Pharm. Res. 2000, 17(8) : 991-998.
Key words : PAMAM dendrimers, oral delivery

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. Cationic PAMAM dendrimers (generations 3 and 4) and anionic PAMAM dendrimers (generations 2.5 and 3.5) that were modified to include on average a single pendant amino group were radioiodinated using the Bolton and Hunter reagent. ¹²⁵I-labelled dendri-mers were incubated with everted sacs in vitro and the transfer of radioactivity into the tissue and serosal fluid was followed with time. The serosal transfer rates seen for all anionic generations were extremely high with Endocytic Indices (EI) in the range 3.4-4.4 ml/mg protein/h. The concentration-dependence of serosal transfer was linear over the dendrimer concentration range 10-100 mg/ml. For ¹²⁵I-labelled generation 5.5 the rate of tissue uptake was higher (EI = 2.48ą0.5 ml/mg protein/h) than seen for ¹²⁵I-labelled generation 2.5 and 3.5 (0.6-0.7 ml/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 ml/mg protein/h) which was higher (p< 0.05) than the rate of serosal transfer (EI = 2.3-2.7 ml/mg protein/h), probably due to nonspecific adsorption of cationic dendrimer to the mucosal surface.

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.

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