CONICET | Buscador de Institutos y Recursos Humanos

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease characterized by cognitive, memory and other mental impairments. There is no cure and is usually terminal. Theworldwide prevalence is 16.94 million. The etiology is multifactorial and poorly understood. Many hypotheses have been proposed; the most accepted are related to a deficiency ofacetylcholine (ACh), the formation of senile plaques of B-amyloid (AB) protein outside the cells and the formation of intracellular neurofibrillary of hyperphosphorylated TAU protein (pTAU).Tacrine (TAC) is an inhibitor of the enzyme acetylcholinesterase which was approved by FDA for the treatment of the symptoms of AD. Due to their hepatotoxicity and its adversepharmacological profile, TAC was removed from the market. Furthermore, carbamazepine (CBZ) is an antiepileptic approved and currently on the market that was shown to potentiatelysosomal autophagy, reducing levels of AB and p-TAU and improving memory in mice models of AD.Dendrimers are three-dimensional polymers bring unique properties to the field of drug delivery systems (DDS). G4 and G4,5 PAMAM dendrimers (positive and negative charge,respectively) are optimal as SDD because drug molecules can be incorporated within their hydrophobic pockets or groups in their surface. The complexed drugs can obtain the SDDphysicochemical properties which would increase significantly their solubility in aqueous media and alter their pharmacokinetics and biodistribution, increasing brain arrival. Therefore theaim of this study was to obtain and characterize complexes between dendrimers and drugs.So far, the complexes were obtained with both drugs and characterized by light scattering and zeta potential. Further, infrared spectroscopy (FTIR) were performed to determine theinteractions between drugs and dendrimers. Also, in vitro drug release was studied using the micro-dialysis method.

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