Structure controlled G5G2.5 tecto-dendrimers: cytotoxicity, uptake and transepithelial transport across Caco-2 cell monolayers

PRISCILA SCHILRREFF, DIANA RONCAGLIA, EDER L. ROMERO AND MARÍA JOSE MORILLA

Conferencia; CLINAM 2011; 2011

Anionic poly(amido amine) (PAMAM) dendrimers generations (G) 1.5 to 3.5 are acknowledged 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. Up to the moment however, the main aspects of their interaction with biological structures remain unknown. Thus in the present work we have synthesized PAMAM G5 core and G2.5 shell tecto-dendrimers (G5G2.5), determined their cytotoxicity and cell uptake, and finally screened their own transepithelial transport across Caco-2 cell monolayers.