Poly-HEMA as a drug delivery device for<i>in vitro</i>neural networks on micro-electrode arrays

Abstract

Delivery of pharmacological agents in vitro can often be a difficult, time consuming and costly process. In this paper, we describe an economical method for in vitro delivery using a hydrogel of poly hydroxyethyl methacrylate (PHEMA) that can absorb up to 50% of its weight of any water-solubilized pharmacological agent. This agent will then passively diffuse into surrounding media upon application in vitro. An in vitro test of PHEMA as a drug delivery device was conducted using dissociated rat-cortical neurons cultured on micro-electrode arrays. These micro-electrode arrays permit the real-time measurement of neural activity at 60 different sites across a network of neurons. Neural activity was compared during the application of PHEMA saturated with cell culture media and PHEMA saturated with bicuculline, a widely used pharmacological agent with stereotypical effects on neural activity patterns. Application of PHEMA saturated with bicuculline produced a gradual increase in concentration in vitro. When the minimum effective concentration of bicuculline was reached, which was found to be 0.59 microM using the diffusion properties of PHEMA, it produced the rapid almost periodic synchronized bursting characteristically associated with this agent. In contrast, the application of PHEMA saturated in culture media alone had no effect on neural activity reinforcing its inherent inert properties. Since PHEMA is nontoxic, can be molded into a variety of shapes, quickly manufactured in any laboratory and is inexpensive to produce, the material represents a promising alternative to drug delivery systems on the market today.