Iontophoresis From a Micropipet into a Porous Medium Depends on the ζ-Potential of the Medium

Abstract

Iontophoresis uses electricity to deliver solutes into living tissue. Often, iontophoretic ejections from micropipettes into brain tissue are confined to millisecond pulses for highly localized delivery, but longer pulses are common. As hippocampal tissue has a ζ-potential of approximately –22 mV, we hypothesized that, in the presence of the electric field resulting from the iontophoretic current, electroosmotic flow in the tissue would carry solutes considerably farther than diffusion alone. A steady state solution to this mass transport problem predicts a spherically symmetrical solute concentration profile with the characteristic distance of the profile depending on the ζ-potential of the medium, the current density at the tip, the tip size and the solute electrophoretic mobility and diffusion coefficient. Of course, the ζ-potential of the tissue is defined by immobilized components of the extracellular matrix as well as cell-surface functional groups. As such, it cannot be changed at will. Therefore, the effect of the ζ-potential of the porous medium on ejections is examined using poly(acrylamide-co-acrylic acid) hydrogels with various magnitudes of ζ-potential, including that similar to hippocampal brain tissue. We demonstrated that nearly neutral fluorescent dextran (3 and 70 kD) solute penetration distance in the hydrogels and OHSCs depends on the magnitude of the applied current, solute properties, and, in the case of the hydrogels, the ζ-potential of the matrix. Steady state solute ejection profiles can be predicted semi-quantitatively.

Quantitative analysis of iontophoretic drug delivery from micropipettes

“…Because the receiving medium can influence the ejected distribution, all ejections were made into the cortex of rat brain slices. 34, 35 To account for differences in ejection quantity, profiles were normalized by the intensity 30 µm from the barrel tip. The normalized spatial distributions for ejections using currents < 200 nA were nearly identical (Figure 1C).…”

Numerical Modeling of Electroosmotic Push–Pull Perfusion and Assessment of Its Application to Quantitative Determination of Enzymatic Activity in the Extracellular Space of Mammalian Tissue

“…The interstitial velocity is the average velocity in the macroscopic direction of flow through the interstitial space of the porous medium. In order to determine the effective charge density, we started with an equation for superficial electroosmotic velocity in a porous medium 33,37 : $$u_{eo}=\frac{{\epsilon }_W\zeta \epsilon }{\eta {\lambda }^2}\nabla \varphi$$where ε w is the permittivity of water (F/m), ζ is the zeta-potential (V), ε is the porosity, and λ is the tortuosity (or $\frac{l}{L}$, where l is the length of the curved path and L is the length of the straight path through the porous medium). By equating the superficial velocities in Eqns.…”

Characterization of Solute Distribution Following Iontophoresis from a Micropipet

“…Introducing the dimensionless distance ρ (ρ = r / a ), this can be written using the Peclet number in a similar manner to Weber and co-workers: 21 where the Peclet number ( Pe ) is a dimensionless value, which for the present work is given by This equation was solved previously using the boundary conditions that C (ρ → ∞) = 0 and J (ρ = 1) are constant. The solution is then where the flux at the boundary of the sphere, J 0 , can be described by where C int is the concentration of the ejected substance in the interior of the barrel.…”