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

ROMINA, ALMIRON; CECILIA, TETTAMANTI; SOFIA, MARTINEZ; MERCEDES, ANTONINO; ALFREDO, LORENZO; DANIEL, ALLEMANDI; DANIELA, QUINTEROS

Simposio; 2nd International Symposium LatBrain Initiative.; 2022

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 Aβ40 fibers. We observe that NP-EB-GAL were effective in reducing the APP interaction with BACE1 induced by Aβ 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 Aβ-induced loss of synaptophysin in primary cortical neurons. These results allow us to validate a method of preparation of NPs-GAL, effective in reducing Aβ toxicity in in vitro models of AD, with potential utility to halt Aβ deposition and neurodegeneration in animal models of disease and with translational possibility in human patients.