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.

Electroosmosis is the bulk fluid flow initiated by application of an electric field to an electrolyte solution in contact with immobile objects with a non-zero ζ-potential such as the surface of a porous medium. Electroosmosis may be used to assist analytical separations. Several gel-based systems with varying electroosmotic mobilities have been made in this context. A method was recently developed to determine the ζ-potential of organotypic hippocampal slice cultures (OHSC) as a representative model for normal brain tissue. The ζ-potential of the tissue is significant. However, determining the role of the ζ-potential in solute transport in tissue in an electric field is difficult because the tissue's ζ-potential cannot be altered. We hypothesized that mass transport properties, namely the ζ-potential and tortuosity, could be modulated by controlling the composition of a set of hydrogels. Thus, poly(acrylamide-co-acrylic acid) gels were prepared with three compositions (by monomer weight percent): acrylamide/acrylic acid 100/0, 90/10, and 75/25. The ζ-potentials of these gels at pH 7.4 are distinctly different, and in fact vary approximately linearly with the weight percent of acrylic acid. We discovered that the 25% acrylic acid gel is a respectable model for brain tissue, as its ζ-potential is comparable to the OHSC. This series of gels permits the experimental determination of the importance of electrokinetic properties in a particular experiment or protocol. Additionally, tortuosities were measured electrokinetically and by evaluating diffusion coefficients. Hydrogels with well-defined ζ-potential and tortuosity may find utility in biomaterials, analytical separations, and as a surrogate model for OHSC and living biological tissues.