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150 | GALLEIN-LOADED NANOPARTICLES OF HUMAN ALBUMIN ARE EFFECTIVE PREVENTING THE TOXIC EFFECTS OF Aβ IN IN VITRO MODELS OF ALZHEIMER’S DISEASE.

Disorders of the Nervous System

Author: ROMINA SOLEDAD ALMIRON | email: ralmiron@immf.uncor.edu


ROMINA SOLEDAD ALMIRON , CECILIA TETTAMANTI , SOFIA MARTINEZ , MAGDALENA  ANTONINO , ALFREDO LORENZO , DANIEL ALLEMANDI , DANIELA QUINTEROS , ELENA ANAHI BIGNANTE

1° INIMEC-CONICET-UNC
2° UNITEFA-UNC

Achieve a good cerebral bioavailability of drugs for treatment of neuropathologies is one of the great challenges of medicine and pharmacotechnics. The objective of this work is the design and in vitro characterization of gallein-loaded nanoparticles of human albumin for further evaluation in vivo models of Alzheimer’s disease (AD) (Antonino et al. 2022). We obtained human serum albumin nanoparticles without and with gallein (GAL) (NP, NP-GAL) by the method of desolvation and thermal stabilization. The incorporation of the Evans Blue (EB) dye did not affect the encapsulation of GAL to the system (NP-EB, NP-EB-GAL) and allowed us to observe its location through the fluorescence that it presents when binding to albumin. We found that NP-EB and NP-EB-GAL entered to N2a cells and rat cortical neurons and adhered to extracellular A?40 fibers. We observe that NP-EB-GAL were effective in reducing the APP interaction with BACE1 induced by A? to the same degree as free GAL did. We also observed the ability of NP-EB-GAL, and interestingly of NP-EB, to reduce neuritic dystrophy and A?-induced loss of synaptophysin in primary cortical neurons. These results allow us to validate a method of preparation of NPs-GAL, effective in reducing A? toxicity in in vitro models of AD, with potential utility to halt A? deposition and neurodegeneration in animal models of disease and with translational possibility in human patients.

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