INVESTIGADORES
MORILLA Maria Jose
congresos y reuniones científicas
Título:
Structure controlled G5G2.5 tecto-dendrimers: transient perturbation on Caco-2 cellular barrier
Autor/es:
SCHILRREFF P, ROMERO EL, MORILLA MJ
Lugar:
Berlin
Reunión:
Conferencia; International conference Tight junctions and their proteins; 2016
Resumen:
Dendrimersare highly branched macromolecules with nanometer-scale dimensions. Small anionic Poly(amidoamine) PAMAM dendrimers are known to cross epithelial barriers by a combination of transcellular and paracellular routes. These small dendrimers are said to induce a transient opening of tight junctions, thereby enhancing their own transport via the paracellular pathway. This unique property makes them promising tools capable of increasing the oral bioavailability of poorly permeable or poorly soluble 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. Tecto-dendrimers G5G2.5 were synthesized, purified, caracterized 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 cellswithoutcausing 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 tight junction perturbation, in the absence of massive cell damage