title: New potential strategies for Alzheimer's disease prevention: pegylated biodegradable dexibuprofen nanospheres administration to APPswe/PS1dE9.
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 β-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.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy, University of Barcelona; Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona.
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez-López
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Ettcheto
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy, University of Barcelona; Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona.
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Egea
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy, University of Barcelona; Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona.
authors.forename: Marta
authors.initials: M
authors.lastname: Espina
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy, University of Barcelona; Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Calpena
authors.affiliation: Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Biochemistry unit, Faculty of Medicine and Health Sciences, University Rovira i Virgili, Reus Tarragona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Folch
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy, University of Barcelona; Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona. Electronic address: marisagarcia@ub.edu.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: García
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002460:Cell Line; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D007052:Ibuprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D054118:Nanospheres / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; C539402:dexibuprofen; D007052:Ibuprofen
keywords: Alzheimer's disease; Blood–Brain barrier; Dexibuprofen; Nanoparticles; Nanospheres; PLGA-Peg