Giora Enden

Ultrasound mediated transdermal drug delivery.

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injections. However, the stratum corneum serves as a barrier that limits the penetration of substances to the skin. Application of ultrasound (US) irradiation to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. This review presents the main findings in the field of sonophoresis in transdermal drug delivery as well as transdermal monitoring and the mathematical models associated with this field. Particular attention is paid to the proposed enhancement mechanisms and future trends in the fields of cutaneous vaccination and gene therapy.

A Numerical Study of Plasma Skimming in Small Vascular Bifurcations

Owing in part to a plasma-skimming mechanism, the distribution of red blood cells (RBCs) into branches of microvascular bifurcations typically differs from the distribution of the bulk blood flow. This paper analyzes the plasma-skimming mechanism that causes phase separation due to uneven distribution of red blood cells at the inlet cross section of the parent vessel. In a previous study, the shape of the surface that divides the flow into the branches was found by numerical simulation of three-dimensional flow of a homogeneous Newtonian fluid in T-type bifurcations. Those findings are used in this study to determine, as a first approximation, the side-to-parent vessel RBC flux ratio and discharge hematocrit ratio as a function of corresponding flow ratios. Calculations are based on the assumption that RBCs move along streamlines of a homogeneous Newtonian fluid and are uniformly distributed within a concentric core at the inlet cross section of the parent vessel. The results of our calculations agree well for a wide range of flow parameters with experimental data from in vivo and in vitro studies.

A numerical study of the shape of the surface separating flow into branches in microvascular bifurcations.

The shape of the separating surface formed by the streamlines entering the branches of microvascular bifurcations plays a major role in determining the distribution of red blood cells and other blood constituents downstream from the bifurcation. Using the finite element method, we determined the shape of the surface through numerical solution of three dimensional Navier-Stokes equations for fluid flow at low Reynolds numbers in a T-type bifurcation of circular tubes. Calculations were done for a wide range of daughter branch to parent vessel diameter ratios and flow ratios. The effect of Reynolds number was also studied. Our numerical results are in good agreement with previously reported experimental data of Rong and Carr (Microvascular Research, Vol. 39, pp. 186-202, 1990). The numerical results of this study will be used to predict the concentration of blood constituents downstream from microvascular bifurcations providing that the inlet concentration profile is known.

Stratified multiphase model for blood flow in a venular bifurcation

Availablein vitro andin vivo experimental observations suggest that red cell aggregation and blood vessel geometry are improtant determinants of the flow characteristics of blood in venules. However, no consistent relationship has been observed between red blood cell aggregation and vascular resistance. The present work attempts to understand this relationship by evaluating computationally the effect of red cell aggregation on the flow characteristics of blood in a converging vessel, bifurcation. The proposed mathematical model considers blood as a two-phase continuum, with a central core region of concentrated red cell suspension that is surrounded by a layer of plasma adjacent to the vessel wall. In the central core region, blood is described by Quemada’s non-Newtonian rheological model, in which local viscosity is a function of both the local hematocrit and a structural parameter that is related to the size of red blood cell aggregates. Fluids from the two feeding branches are immiscible, which results in a stratified multiphase flow in the collecting venule. Calculations predict a complex, three-dimensional pattern of blood flow and generally nonaxisymmetric distribution of velocity, hematocrit, and shear stress in the collecting venule. The calculations are a first step toward a realistic model of blood flow in the venous microcirculation.

Converging three-dimensional stokes flow of two fluids in a T-type bifurcation

Studies of three-dimensional Stokes flow of two Newtonian fluids that converge in a T-type bifurcation have important applications in polymer coextrusion, blood flow through the venous microcirculation, and other problems of science and technology. This flow problem is simulated numerically by means of the finite element method, and the solution demonstrates that the viscosity ratio between the two fluids critically affects flow behaviour. For the parameters investigated, we find that as the viscosity ratio between the side branch and the main branch increases, the interface between the merging fluids bulges away from the side branch. The viscosity ratio also affects the velocity distribution: at the outlet branch, the largest radial gradients of axial velocity appear in the less-viscous fluid. The distribution of wall shear stress is non-axisymmetric in the outlet branch and may be discontinuous at the interface between the fluids.

An analytical solution for steady flow of a Quemada fluid in a circular tube

An analytical solution is obtained for steady flow of Quemada-type fluids in a circular tube driven by a constant pressure gradient. Expressions are derived for velocity distribution and for volumetric flow rate as a function of pressure gradient or wall shear stress.

Harvesting Low Molecular Weight Biomarkers Using Gold Nanoparticles.

We developed and characterized a platform based on gold (Au) nanoparticles (NPs) coated with poly(acrylic acid) (PAA) for harvesting positively charged, low molecular weight (LMW) proteins. The particles are synthesized using a layer by layer (LbL) procedure: first the gold NPs are coated with positively charged polyethylenimine (PEI) and subsequently with PAA. This simple procedure produces stable PAA-PEI-Au (PPAu) NPs with high selectivity and specificity. PPAu NPs successfully harvested, separated, and detected various LMW proteins and peptides from serum containing a complex mixture of abundant high molecular weight (HMW) proteins, including bovine serum albumin (BSA) and Immunoglobulin G (IgG). In addition, PPAu NPs selectively harvested and separated LMW proteins from serum in the presence of another positively charged competing protein. Furthermore, PPAu NPs successfully harvested a LMW biomarker in a mock diseased state. This system can be applied in various biomedical applications where selective harvesting and identifying of LMW proteins is required. A particularly useful application for this system can be found in early cancer diagnosis as described hereinafter.

A Numerical Simulation of the Flow in a T-Type Bifurcation and Its Application to an “End to Side” Fistula

Some recent surgical procedures such as arteriovenous fistula, or coronary and cerebral by-passes were observed to yield counterdirectional branching blood flows. There is a lack of knowledge about the role of the counterdirectional flow ratio, the angle of anastomosis and the shear stresses in the process of thrombogenesis that leads to shunt occlusion. The program developed to simulate these hemodynamic conditions uses an efficient numerical scheme for the solution of the 2-D Navier-Stokes equations and can be easily adapted to flows in other geometrical configurations.

New doxorubicin nanoparticles engineered from calcium-crosslinked carbomer and a microemulsion precursor

Abstract The purpose of this study was to investigate a new polymeric system and production process in which self-assembled doxorubicin-loaded nanoparticles were synthetized by using a water-in-oil microemulsion as a template and calcium ions as cross-linkers. The manufacturing process combined cross-linking of carbomer within a W/O microemulsion followed by a phase-separation technique to avoid using organic solvents for extraction. To assess the sustained release behavior of doxorubicin from the nanoparticles, we have developed a new simple method based on the permeability coefficient of a synthetic membrane mounted on Franz diffusion cell system. Franz cells were preferred over the commonly used dialysis tubing because they provide adequate measures of the diffusion area as well as the volumes of the media in both sides of the membrane. The lower permeability values obtained for nanoparticles have shown that the release is a limiting step of the diffusion process, while the calculated straight lines may imply that the apparent release rate of the nanoparticle ensembles is close to a zero-order kinetics. The new drug release method for the evaluation of nano-carriers, utilizing a simple linear model to determine the permeability coefficient, has been proposed for perfect sink and non-sink conditions.