Structure controlled G5G2.5 tecto-dendrimers: transient perturbation on Caco-2 cellular barrier

PRISCILA SCHILRREFF; EDER L. ROMERO; MARÍA J. MORILLA

Conferencia; International conference Tight junctions and their proteins; 2016

Nanomedicine Research Program, National University of Quilmes, Buenos Aires, ArgentinaDendrimers are nano-sized highly branched macromolecules. Small anionic Poly(amidoamine) PAMAM dendrimers are known to cross epithelial barriers by inducing a transient opening of tight junctions (TJ), thereby enhancing their own transport via the paracellular pathway. This property makes them promising tools capable of increasing the oral bioavailability of poorly permeable molecules. On the other hand, PAMAM dendrimers can be used as bricks to construct a new class of polymers known as tecto-dendrimers. These polymers exhibit a higher architectonic order than single dendrimers and are composed of a central dendrimer with multiple dendrimers attached to its periphery. The exhibition of multiple small dendrimers on the surface could lead tecto-dendrimers to overcome the single capacity of dendrimers to interact with TJ and increase their transepithelial transport across cell monolayers. In the present work we have synthesized PAMAM G5 core and G2.5 shell tecto-dendrimers (G5G2.5). They were exhaustively characterized and their transepithelial transport across Caco-2 cell monolayers was evaluated. Our results showed that although less cytotoxic than core cationic dendrimers, transepithelial transport of tecto-dendrimers was not greater than that of single anionic dendrimers. All dendritic polymers reduced the transepithelial electrical resistance on Caco-2 cells without causing significant release of LDH. Nevertheless, an increased permeability of Lucifer yellow was shown when with it was co-incubated with tecto-dendrimers. If well the higher size of tecto-dendrimers as compared to small single dendrimers could impair their passage across tight junctions, an increased permeability of small molecules could be interpreted as the induction of a TJ perturbation, in the absence of massive cell damage.