Vincent Regnier

Buoyant-thermocapillary instabilities in medium-Prandtl-number fluid layers subject to a horizontal temperature gradient

Abstract Coupled buoyant and thermocapillary instabilities in a fluid layer of infinite horizontal extent bounded below by a rigid plane and above by a free flat surface and submitted to a temperature gradient are investigated. A general 3D mathematical formulation is used to determine the linearized perturbated equations of the steady state induced by the temperature gradient. Numerical results are obtained in the case of a horizontal temperature gradient, lower and upper surfaces are adiabatically isolated and the range of variation of the Prandtl number is selected as [10−2, 10]. The presence of travelling rolls is exhibited. The results display three kinds of behaviour according to the values taken by the Prandtl number: (a) 4 × 10−3 2.6.

Localization of a FITC-Labeled Phosphorothioate Oligodeoxynucleotide in the Skin After Topical Delivery by Iontophoresis and Electroporation

AbstractPurpose. The aim of this study was to verify the hypothesis that the application of high voltage to the skin enhances both stratum corneum and keratinocyte permeability. Therefore, the transport of FITC labelled phosphorothioate oligonucleotides (FITC-PS) administered by passive diffusion, iontophoresis or electroporation was localized. Methods. Fluorescent microscopy and laser scanning confocal microscopy were used to visualize the FITC-PS transport at the tissue and cell level respectively in hairless rat skin after electroporation (5 × (200 V ∼ 500 ms) or iontophoresis (same amount of charges transferred). Results. FITC-PS did not penetrate the viable skin by passive diffusion. Molecular transport in the skin upon electroporation or iontophoresis was localized and implied mainly hair follicles for iontophoresis. In the stratum corneum, the pathways for FITC-PS transport were more transcellular during electroporation and paracellular during iontophoresis. FITC-PS were detected in the nucleus of the keratinocytes a few minutes after pulsing. In contrast, iontophoresis did not lead to an uptake of the oligomer. Conclusions. The internalization of FITC-PS in the keratinocytes after electroporation confirms the hypothesis and suggests that electroporation, which allows both efficient topical delivery and rapid cellular uptake of the oligonucleotides, might be useful for antisense therapy of epidermal diseases.

Mechanisms of a phosphorothioate oligonucleotide delivery by skin electroporation.

Skin electroporation has great potential for topical delivery of oligonucleotides. Controled therapeutic levels of an intact phosphorothioate oligonucleotide (PS) can be reached in the viable tissue of the skin. The aim of this work was to investigate the transport mechanisms of a PS in hairless rat skin by electroporation, and hence to allow optimization of oligonucleotides (ONs) topical delivery. The pulsing condition used was five exponentially-decaying pulses of 100 V and 500 ms pulse time. The main mechanism of PS transport in the skin viable tissues during pulsing was electrophoresis. The electroosmosis contribution was negligible. Electrophoresis created within minutes a reservoir of PS in the skin viable tissues, which persisted within a therapeutic range of hours. A strong PS/stratum corneum interaction occurred.

Parameters controlling topical delivery of oligonucleotides by electroporation.

Electroporation, using high voltage electrical pulses has been recognized as a powerful method for delivering macromolecules such as DNA and proteins in cells, or smaller molecules through the skin. Transdermal electroporation could combine targeted delivery of drugs to the skin and permeabilization of skin cells, suggesting that electroporation could be an interesting alternative for topical delivery of oligonucleotides. This work is devoted to the determination of the electroporation parameters that allow optimal delivery of oligonucleotides to the viable tissues of hairless rat skin in vitro. Phosphorothioate derivatives were preferred to the phosphodiester congeners as the former were found to be much less degraded when extracted from the tissues. Long duration (100-500 ms)--medium voltage (100-200 V)--exponentially decaying pulses appeared to be the best conditions for delivering oligonucleotides to the skin. The oligonucleotide quantity permeating the viable tissues of the skin was controlled by the selection of the electrical parameters of the pulses (voltage, pulse time and number of pulses) or by the ON concentration in the donor compartment. After delivery by electroporation, therapeutic levels of oligonucleotides were reached in the viable tissues of the skin (above 1 microM or 10 microM in intact or stripped skin respectively). Taken together, our results show that electroporation could be an interesting method for the delivery of oligonucleotides to the skin.

Linear and nonlinear Rayleigh–Bénard–Marangoni instability with surface deformations

Thermoconvective instabilities in a bilayer liquid–gas system with a deformed interface are investigated. In the first part of the work which is devoted to a linear approach, emphasis is put on the role of the upper gas layer on the instability phenomenon. The condition to be satisfied by the gas to remain purely conductive is established. The so-called Oberbeck–Boussinesq approximation is discussed and its range of validity is carefully defined. Instead of the classical Rayleigh, Marangoni, crispation, and Galileo numbers, new dimensionless groups are introduced. A critical comparison with several previous works is made. The nonlinear analysis consists in studying the different convective patterns which can appear above the threshold. Particular attention is devoted to the shape of the interface and the so-called “hybrid” relief. The amplitude of the deformation is also determined and comparison with experimental data is discussed.

Role of interface deformations in Benard-Marangoni instability

Abstract This work is concerned with a linear analysis of natural thermoconvection in a two-layer system formed by a liquid surmounted by an upper immiscible gas layer (Benard-Marangoni problem). Emphasis is put on the role of the air layer on the thermoconvective instability. It is shown that the motion inside the gas phase can be disregarded provided its thickness is smaller than the thickness of the liquid layer. The gas can then be modelled as a purely conductive medium. Another important problem discussed here is the role of surface deformations on the onset of convection. In that respect, the use of Boussinesqs approximation is discussed and its limits of validity are specified. The main results are the following. First, it is concluded that overstability cannot be observed in ordinary fluids under realistic experimental conditions. Besides, it is shown that, among the relatively larger number of parameters appearing in the problem, the viscosity is by far the most important. Moreover, new dimensionless numbers are introduced to better apprehend the physical context. The experimental conditions required to observe the surface zero-wave number instability are also determined, as well as the conditions under which gravity effects may be neglected on earth. Finally it is examined under which circumstances the interface can be considered as remaining flat.

Comparison of Iontophoresis and Electroporation: Mechanisms and Tolerance

Drug delivery across skin offers a non invasive, user-friendly alternative to conventional route of administration. However, the skin’s outer layer, the stratum corneum is an extremely effective barrier which prevents transports of most drugs at therapeutic rate. Chemical and physical approaches have been investigated to increase and extend transdermal transport.