Electron microscopic analysis of nanoparticles delivering thioflavin-T after intrahippocampal injection in mouse: implications for targeting beta-amyloid in Alzheimer's disease.
Prevention of beta-amyloid (Abeta) production, aggregation and formation of Abeta deposits is a key pharmacological target in Alzheimer's disease. The passage of Abeta-binding compounds through the blood-brain barrier is often hampered for free ligands, whereas it is enhanced by drug encapsulation in nanoparticles. Here, we describe the preparation and characterization of polymeric carriers containing thioflavin-T as a marker for fibrillar Abeta. This study is then focused on electron microscopic analyses of thioflavin-T after injection of thioflavin-T-containing nanoparticles into the mouse hippocampus. Therefore, the photoconversion of fluorescent thioflavin-T as model drug was performed in tissues fixed 3 days post-injection. Thioflavin-T delivered from nanospheres was predominantly found in neurons and microglia. Our data suggest that drugs delivered by nanoparticles might target Abeta in the brain.
Härtig
Wolfgang
W
Department of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany.
Paulke
Bernd R
BR
Varga
Csaba
C
Seeger
Johannes
J
Harkany
Tibor
T
Kacza
Johannes
J
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004659:Enbucrilate / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage*; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure*; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D036103:Nanotechnology; D010316:Particle Size; D011108:Polymers; D011137:Polystyrenes / Q000138:chemical synthesis / Q000737:chemistry*; D013844:Thiazoles / Q000008:administration & dosage*
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D004337:Drug Carriers; D005456:Fluorescent Dyes; D011108:Polymers; D011137:Polystyrenes; D013844:Thiazoles; C473120:butylcyanoacrylate-graft-polystyrene; C009462:thioflavin T; D004659:Enbucrilate