New potential strategies for Alzheimer's disease prevention: pegylated biodegradable dexibuprofen nanospheres administration to APPswe/PS1dE9

Identifier:  imarina:5130798

Handle: https://hdl.handle.net/20.500.11797/imarina5130798

Authors:  Sánchez-López, E; Ettcheto, M; Egea, MA; Espina, M; Calpena, AC; Folch, J; Camins, A; García, ML

Abstract:
Dexibuprofen loaded pegylated poly(lactic-co-glycolic) nanospheres prepared by solvent diffusion method were designed to increase Dexibuprofen brain delivery reducing systemic side effects. Nanospheres exhibited a mean particle size around 200 nm (195.4 nm), monomodal population and negative surface charge. Drug loaded nanospheres showed a sustained release profile, allowing to modify the posology in vivo. Nanospheres were non-toxic neither in brain endothelial cells nor astrocytes and do not cause blood¿brain barrier disruption. Nanospheres were able to partially cross the cells barrier and release the drug after co-culture in vitro experiments, increasing Dexibuprofen permeation coefficient. Behavioral tests performed in APPswe/PS1dE9 mice (mice model of familial Alzheimer's disease) showed that nanospheres reduce memory impairment more efficiently than the free drug. Developed nanospheres decrease brain inflammation leading to ¿-amyloid plaques reduction. According to these results, chronical oral Dexibuprofen pegylated poly(lactic-co-glycolic) nanosystems could constitute a suitable strategy for the prevention of neurodegeneration.