Delivery of SPMNMs to CNS of rodents with artificially provoked epileptic seizures

I. Introduction

Our research group is formulating a manifold strategy, according to which, first, the SPMNMs aggregates will be given an aspect ratio (i.e. rods) to allow orientation of the sub micron rods, under the effect of a μT magnetic moment. This orienting effect requires the use of a simple homogeneous magnetic field (parallel field lines) with low intensity, the kind of magnetic fields used found in epileptic focus. Resorting to the use of magnetic moments instead of magnetic force (geometrical gradient) is more likely to match the scenario met when pyramidal cells are propagating seizure like electrical activity. Delivery of SPMNPs to CNS has been demonstrated using polymeric coating that are not reliable from a magnetic performance point of view, nor are the delivery techniques that rely on disruption of the BBB using focused ultrasound, due to the infectious risque that it entails. Part of our research hypothesis thus is the feasibility of bare SPMNMs through the BBB using static magnetic fields generated by Niodim-Yag permanent magnets attached to the head of the rodent at the time odf the intravenous delivery of the theragnostic agent.

II. Motivation • Can any shape SPM NM reach the CNS without polymeric coating and under the effect of an external magnetic field. • Answering this question is laying out the way for delivery technologies using the MRI's system strong and static magnetic field. • Could submicron rods be oriented in under the μT neuronal magnetic field • Magnetic moment driven aggregation of SPMNMs requires parallel field lines ( neither convergent nor divergent thus no specific region of the brain is concerned). • One new property is that nanorods exhibit is the fact that they are the most appropriate for use in presence of a magnetic field such as those present in an MRI system. • Experimental work will be run on rats inoculated with epileptic precursors and no symptomatic conditions like disrupted BBB or blood hypotension

III. Hypothesis

When seizures take place, μT magnetic moments are able to orient the nanorods. Whereas in the rest of the brain, the fluid shear forces dominate and electric currents due to normal brain activity produce transient magnetic field that have no noticeable effect on the aggregation coefficient of NPs nor on the orientation of the NRs. Part of this study is to quantize the aggregation coefficient at the epileptic focus using rotational (rods & moments) and translational (particles & gradients) forces.

1) A static magnetic field applied on the scalp will allow delivery of SPMNM to CNS 2) The ratio of fluids shear forces on the SPM Poly/Met nanorod's surface to the magnetic moment generated by internal currents flow in pyramidal cells will depend on the position of the nanorod relatively to the epileptic focus.

IV. Materials and methods

Given well characterized SPM nanoparticles and SPM Polmeric or Metalic nanorods suspension in water.(purchased materials). In order to mimic MRI contrast agents like Gd(III) a concentration of 5 mg/m has to be prepared by dilution. We will carry out the following experiments based on t size and dispersion.

4.1 In vivo experiments on the delivery of SPMNMs to rats CNS in submerged in a MRI static magnetic field

The following experiment is conducted first using head mounted magnets. The delivery of particles to the brain due to magnetic influence on the BBB or the complex (BBB and Nps) will be elucidated. MRI will show hypointese regions in rat brains that account for successful delivery of the NPs. In the second series of experiments, rats that were injected with the NPs in the past and that showed a history of epileptic activity following inoculation with epileptic triggering compounds, will be subjected to MRI protocol at different periods of time. Depending on the number of seizures, the aggregates will be more or less detectable. The focus will reveal its self after a right number of Nps has been deposited or trapped by the magnetic fields it harbours. Further studies are envisaged to explain the mechanism of retention of the NPs at the site of the focus. particles that will not deposit by the μT magnetic agglomeration will be cleared or biodegraded to join the naturally occurring brain iron in its fate.

4.2 Parameters • Intensity and location of static magnetic field of the permanent Niodim-Yag magnets • SPMNPs magnetic moment and size and crystal structure • Polymeric SPMNRs asperct ratio and porosity and density of magnetic cores • Metalic SPMNRs asperct ratio, criystal structure and magnetic moment • number of injection times • number of epileptic seizurs

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Optical Characterization Of A Cantilever Array : Toward Integrated Wave Front Correctors And Analyzers For Miniaturized Adaptive Optics Systems

This paper presents the design, optimization and optical characterization of an array electrostatic actuators based MEMS to be used as an adaptive optics component of a portable retinal imaging device. The proposed wave-front corrector is implemented in (CMC) polymump technology and features an array of cantilevers on which planar reflective gold thin films were deposited for characterization purposes. The cantilevers relative deflections will be set based on the output of a wave-front analyzer to correct higher order optical aberrations. For the sake of achieving precise wave front correction, three cantilever sizes were implemented on the chip for a total of 64 cantilevers that will serve as actuators of a deformable mirror in future work. Array of actuators are hindered by the off-plane initial misalignment phenomenon caused by thin films deposition process and mismatches between the cantilevers displacement due to size nonuniformities introduced by the fabrication process. The device total surface is XXX × XXX mm2. The COMSOL simulation of the modeled Large, medium and small size cantilevers predicted maximum deflections of 6, 4 and 2 um respectively at maximum DC voltages of XXX, XXX and XXX respectively. These values are verified by laser interferometry and shown that they can be considerably augmented by omitting the gold deposited layer in future versions of the device.