Electron microscopic analysis of nanoparticles delivering thioflavin-T after intrahippocampal injection in mouse: implications for targeting beta-amyloid in Alzheimer's disease |
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Authors: | Härtig Wolfgang Paulke Bernd R Varga Csaba Seeger Johannes Harkany Tibor Kacza Johannes |
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Affiliation: | Department of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany. |
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Abstract: | 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. |
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