CONICET | Buscador de Institutos y Recursos Humanos

Dendrimers are polymers that consist of a core, branches covalently bonded to this core and a surface with multiple terminal groups. Due to their properties, the dendrimers are widely used in the area of nanomedicine. In this work, we used polyamidoamine (PAMAM) dendrimers with ethylenediamine core of generation 4.0 (DG4.0, cationic) and generation 4.5 (DG4.5, anionic). To characterize the ability of both dendrimers to interact with drugs, in this work we studied the formation of complexes with the hydrophobic drugs carbamazepine (CBZ) and curcumin (CUR), and with the hydrophilic drug tacrine (TAC). We developed a protocol to obtain complexes with each type of dendrimers and different drugs. In the case of hydrophobic drugs, different dendrimer-drug ratios were evaluated to increase solubility; while for the hydrophilic drug, only a high ratio was evaluated to ensure interaction. To address the characterization of these complexes, we studied the load capacity (moles of drug per mole of dendrimer) and the ability to increase the water solubility and stability of drugs. Both dendrimers increased CBZ and CUR solubility. Regarding interaction with TAC, they also increased its solubility although it was not significant. In the case of CBZ, dendrimermediated solubilization would be due to the formation of complexes by encapsulating the drug in the internal pockets, involving hydrogen and hydrophobic bridge interactions. In the case of CUR, dendrimer-mediated solubilization could be due to the formation of complexes both by encapsulation in the internal pockets and by anchoring to their surface groups. In the case of TAC, although there was no significant increase in solubility, it was shown that the anionic terminal groups of DG4.5 were able to anchor the cationic amine group of this drug. These results show that the drug-dendrimer interaction is highly dependent on the chemical structure and size of the drug, and the type of dendrimer.