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 beta peptides (Abeta). These polymer colloids are composed of a polystyrene core and a degradable PBCA [poly(butyl-2-cyanoacrylate)] shell with a diameter of 90-100nm 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 7-14 months old APP/PS1 mice with age-dependent beta-amyloidosis, thioflavins selectively targeted fibrillar Abeta 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 Abeta in the brain.
Subject(s)
Amyloid beta-Protein Precursor/metabolism , Amyloid/metabolism , Drug Delivery Systems , Hippocampus/drug effects , Neurofibrillary Tangles/drug effects , Thiazoles/administration & dosage , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/genetics , Animals , Benzothiazoles , Disease Models, Animal , Dose-Response Relationship, Drug , Hippocampus/metabolism , Mice , Mice, Transgenic , Nanostructures , Neurofibrillary Tangles/metabolism , Protein Binding/drug effects , Time FactorsABSTRACT
Low energy ion implantation in polybithiophene (thickness 200 nm) forms a 20 nm thin modified surface layer. Combining surface analysis and electrochemical methods a non destructive depth resolved investigation of the properties of the implanted layer was performed. The composition of the modified layer is dependent on the implanted species: N causes doping, O has a sputtering effect. The modified layer acts as an electronic and ionic barrier as shown by cyclic voltammetry and electron transfer reactions. The effectivity of barrier formation is dependent on the sample pretreatment and the redox state. For reduced samples the redox charge increases for repeated voltammograms (regeneration effect). The according dose dependent band scheme shows an increasing surface resistivity for low doses. At high doses the surface resistivity decreases again due to graphitization. By application of a microstructured mask the polybithiophene was structured within a microm range. Laterally high resolving methods revealed sharp interfaces between implanted and pristine surface ranges. The doping pattern and the electronic properties are localized and do not alter even in an electrolyte. So conducting polymers can be microstructured to give stable structures with changed composition and modified electronic and ionic properties as required for microtechnological applications.
