Tissue electroporation: quantification and analysis of heterogeneous transport in multicellular environments.

Although electroporation is gaining increased attention as a technology to enhance clinical chemotherapy and gene therapy of tissues, direct measurements of electroporation-mediated transport in multicellular environments are lacking. In this study, we used multicellular tumor spheroids of DU145 prostate cancer cells as a model tissue to measure the levels and distribution of molecular uptake in a multicellular environment as a function of electrical and other parameters. These measurements, and subsequent analysis, were used to test the hypothesis that cells in a multicellular environment respond to electroporation in a heterogeneous manner that differs from isolated cells in suspension due to differences in cell state, local solute concentration, and local electric field.

Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies.

Arrays of micrometer-scale needles could be used to deliver drugs, proteins, and particles across skin in a minimally invasive manner. We therefore developed microfabrication techniques for silicon, metal, and biodegradable polymer microneedle arrays having solid and hollow bores with tapered and beveled tips and feature sizes from 1 to 1,000 microm. When solid microneedles were used, skin permeability was increased in vitro by orders of magnitude for macromolecules and particles up to 50 nm in radius.