title: Interaction of selegiline-loaded PLGA-b-PEG nanoparticles with beta-amyloid fibrils.
abstract: Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disease that is caused by the irreversible loss of neurons in the hippocampus and cortex regions of the brain. Although the molecular mechanism of the disease is still unclear, the deposition of the amyloid beta proteins (senile plaques) in the extracellular synaptic spaces of the neocortex is suggested to play a major role in progress of AD. The increased activity of monoamine oxidase-B (MAO-B) in AD brains was suggested to cause oxidative damage, and MAO-B inhibitors have been reported to inhibit the neuronal degeneration. Selegiline, a selective MAO-B inhibitor, known to have beneficial effects in the brain regions which are rich by dopamine receptors, however, studies based on brain targeting of selegiline are limited. Since some recent studies showed the possible Aβ-fibril destabilizing effects of MAO inhibitors, present study was designed to (1) prepare the selective MAO-B inhibitor selegiline-loaded Poly (lactic-co-glycolic acid)-poly (ethylene glycol) (PLGA-b-PEG) nanoparticles (2) to investigate the in vitro Aβ-fibril destabilizing effect of the loaded particles. Selegiline-loaded PLGA-b-PEG nanoparticles were prepared by water-in-oil-in-water (W/O/W) emulsion solvent evaporation method. Destabilizing effect of these particles on the β-amiloid fibril (Aβ 1-40 and Aβ 1-42) formation was determined in vitro by evaluating the decrease in ThT fluorescence intensity and verified by AFM images. Nanoparticle prepared with 5 mg selegiline was found to be the one with highest encapsulation efficiency. Particle size and polydispersity index for this formulation were determined as 217 ± 15.5 nm and 0.321, respectively. For both fibril types, destabilizing effect were found to be increased by increasing incubation time until 6 h; and reached a plateau after the 6 h. Data showed that selegiline-loaded PLGA-b-PEG nanoparticles seem to be a promising drug carrier for destabilizing the β-amiloid fibrils in Alzheimer patients.
authors: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey.
authors: Ipek
authors: I
authors: Baysal
authors: Samiye
authors: S
authors: Yabanoglu-Ciftci
authors: Yeliz
authors: Y
authors: Tunc-Sarisozen
authors: Kezban
authors: K
authors: Ulubayram
authors: Gulberk
authors: G
authors: Ucar
mesh_terms: D000682:Amyloid / Q000187:drug effects*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D004337:Drug Carriers / Q000627:therapeutic use; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D053758:Nanoparticles / Q000008:administration & dosage; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012642:Selegiline / Q000627:therapeutic use*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012642:Selegiline; D019344:Lactic Acid; D011092:Polyethylene Glycols