http://drugdelivery.chbe.gatech.edu/Papers/2004/Prausnitz%20ADDR%202004.pdf

Microneedles for transdermal drug delivery.

The past twenty five years have seen an explosion in the creation and discovery of new medicinal agents. Related innovations in drug delivery systems have not only enabled the successful implementation of many of these novel pharmaceuticals, but have also permitted the development of new medical treatments with existing drugs. The creation of transdermal delivery systems has been one of the most important of these innovations, offering a number of advantages over the oral route. In this article, we discuss the already significant impact this field has made on the administration of various pharmaceuticals; explore limitations of the current technology; and discuss methods under exploration for overcoming these limitations and the challenges ahead.

Current status and future potential of transdermal drug delivery

Microneedles for drug and vaccine delivery.

Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery

Dissolving microneedles for transdermal drug delivery.

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 μm. 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. Intracellular delivery of molecules into viable cells was also achieved with high efficiency. Hollow microneedles permitted flow of microliter quantities into skin in vivo, including microinjection of insulin to reduce blood glucose levels in diabetic rats.

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

Quantitative Study of Electroporation-Mediated Molecular Uptake and Cell Viability

http://drugdelivery.chbe.gatech.edu/Papers/2004/Canatella%20Biophys%20J.%202004.pdf

Tissue Electroporation: Quantification and Analysis of Heterogeneous Transport in Multicellular Environments

Electroporation has been shown to be a powerful method to temporarily disrupt biological barriers and thereby enhance drug delivery. However, incomplete understanding of electroporation mechanisms and dependence on electrical parameters has limited quantitative predictions of molecular uptake and cell viability. To provide a rational basis for designing electroporation protocols we used flow cytometry to quantify uptake and viability for more than 200 different experimental conditions over a range of field strengths, pulse lengths, number of pulses, and cell and solute concentrations with single-cell suspensions. Semi-empirical models were then developed and used to optimize electroporation protocols. With the ultimate goal of electroporating tissues, our single-cell methods were extended to multicellular tumor spheroids to study the effects of increasing biological complexity. Spheroids mimic tumor microregions where drug delivery to the interior cells is more difficult due to poor vascular supply. Their symmetric nature allows for cell layers to be stripped off concentrically so that each layer can be analyzed separately. Combined with confocal microscopy, this study shows that the inner layers of the spheroid are more susceptible to electroporation potentially due to changes in cell state due to nutrient deprivation. These results are being used to develop a rational approach for designing in vivo electroporation protocols.

Paul J. Canatella

Papers

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

Quantitative Study of Electroporation-Mediated Molecular Uptake and Cell Viability

Tissue Electroporation: Quantification and Analysis of Heterogeneous Transport in Multicellular Environments

Electroporation of prostate cancer cells for drug delivery