Thioflavins released from nanoparticles target fibrillar amyloid ? in the hippocampus of APP/PS1 transgenic mice - Analytical Methods & Tools for Lyophilization

Thioflavins released from nanoparticles target fibrillar amyloid ? in the hippocampus of APP/PS1 transgenic mice
Available online 28 December 2005.
T. Siegemunda, b, B.-R. Paulkec, H. Schmiedelb, N. Bordaga, A. Hoffmannd, T. Harkanye, H. Tanilaf, J. Kaczad and W. Hârtiga,
International Journal of Developmental Neuroscience
Volume 24, Issues 2-3 , April-May 2006
ScienceDirect
aDepartment of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, D-04109 Leipzig, Germany
bInstitute of Physics and Earth Science, Soft Matter Physics, University of Leipzig, Leipzig, Germany
cFraunhofer Institute of Applied Polymer Research, Golm, Germany
dDepartment of Histology and Embryology, Institute of Veterinary Anatomy, University of Leipzig, Leipzig, Germany
eLaboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
fDepartment of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland
Abstract
For the delivery of drugs into the brain, the use of nanoparticles as carriers has been described as a promising approach. Here, we prepared nanoparticles as carriers for the model drugs thioflavin T and thioflavin S that bind fibrillar amyloid ? peptides (A?). These polymer colloids are composed of a polystyrene core and a degradable PBCA [poly(butyl-2-cyanoacrylate)] shell with a diameter of 90Ò100 nm as shown by dynamic light scattering. Fluorescence spectrophotometric analysis revealed that encapsulated thioflavin T exhibited significantly stronger fluorescence than the free fluorophore. The enzymatic degradation of core-shell nanoparticles, as required in vivo, was shown after their treatment with porcine liver esterase, a non-specific esterase, in vitro. Shells of nanoparticles were dose-dependently degraded while their polystyrene cores remained intact. In the cortices of 7Ò14 months old APP/PS1 mice with age-dependent ?-amyloidosis, thioflavins selectively targeted fibrillar A? after biodegradation-induced release from their nanoparticulate carriers upon intracerebral injection. Collectively, our data suggest that core-shell nanoparticles with controlled degradation in vivo can become versatile tools to trace and clear A? in the brain.
Keywords: Alzheimer's disease; Drug delivery; Drug targeting; Dynamic light scattering; Senile plaque

Corresponding author. Tel.: +49 341 97 25772; fax: +49 341 97 25749.
You can view the abstract online. A subscription is required to view the full text or it can be purchased online.