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The therapeutic effects of curcumin in treating Alzheimer's disease (AD) depend on the ability to penetrate the blood-brain barrier. The latest nanoparticle technology can help to improve the bioavailability of curcumin, which is affected by the final particle size and stability. We developed a stable curcumin nanoparticle formulation to test in vitro and in AD model Tg2576 mice. Flash nanoprecipitation of curcumin, polyethylene glycol-polylactic acid co-block polymer, and polyvinylpyrrolidone in a multi-inlet vortex mixer, followed by freeze drying with β-cyclodextrin, produced dry nanocurcumin with mean particle size <80 nm. Nanocurcumin powder, unformulated curcumin, or placebo was orally administered to Tg2576 mice for 3 months. Before and after treatment, memory was measured by radial arm maze and contextual fear conditioning tests. Nanocurcumin produced significantly (p=0.04) better cue memory in the contextual fear conditioning test than placebo and tendencies toward better working memory in the radial arm maze test than ordinary curcumin (p=0.14) or placebo (p=0.12). Amyloid plaque density, pharmacokinetics, and Madin-Darby canine kidney cell monolayer penetration were measured to further understand in vivo and in vitro mechanisms. Nanocurcumin produced significantly higher curcumin concentration in plasma and six times higher area under the curve and mean residence time in brain than ordinary curcumin. The P(app) of curcumin and tetrahydrocurcumin were 1.8×10(-6) and 1.6×10(-5)cm/s, respectively, for nanocurcumin. Our novel nanocurcumin formulation produced highly stabilized nanoparticles with positive treatment effects in Tg2576 mice.

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Peripheral vascular disease (PVD) is a common condition often associated with cardiovascular risk factors and events. With the aid of B-mode ultrasound scanning, evidence is emerging that these risk factors and events are significantly related to an increased carotid and femoral intima-media thickness (IMT). More importantly, treatment of these risk factors is associated with a decrease or a diminished progression of the IMT, paralleled by a reduction in cardiovascular events and an improvement in the symptoms associated with PVD. This evidence is particularly strong for lipid lowering therapy. Additional predictors of cardiovascular risk like the IMT, could now influence the decision to intervene with medication.

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This paper presents a fully implantable 100-channel neural interface IC for neural activity monitoring. It contains 100-channel analog recording front-ends, 10 multiplexing successive approximation register ADCs, digital control modules and power management circuits. A dual sample-and-hold architecture is proposed, which extends the sampling time of the ADC and reduces the average power per channel by more than 50% compared to the conventional multiplexing neural recording system. A neural amplifier (NA) with current-reuse technique and weak inversion operation is demonstrated, consuming 800 nA under 1-V supply while achieving an input-referred noise of 4.0 µVrms in a 8-kHz bandwidth and a NEF of 1.9 for the whole analog recording chain. The measured frequency response of the analog front-end has a high-pass cutoff frequency from sub-1 Hz to 248 Hz and a low-pass cutoff frequency from 432 Hz to 5.1 kHz, which can be configured to record neural spikes and local field potentials simultaneously or separately. The whole system was fabricated in a 0.18-µm standard CMOS process and operates under 1 V for analog blocks and ADC, and 1.8 V for digital modules. The number of active recording channels is programmable and the digital output data rate changes accordingly, leading to high system power efficiency. The overall 100-channel interface IC consumes 1.16-mW total power, making it the optimum solution for multi-channel neural recording systems. Index Terms-Multi-channel neural recording system, biomedical application, high power efficiency, power and area trade-off, dual S/H, low-noise neural amplifier, current reuse, NEF, SAR ADC, capacitor-less LDO I. INTRODUCTION imultaneous recording of neuropotentials from the brain over a large number of electrodes provides an effective Manuscript received September 28, 2012.