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Gregory S. Schultz, PhD, is a professor of obstetrics and gynecology, and director of the Institute for Wound Research at the University of Florida (UF). His research has been funded by grants from the National Institutes of Health. He has published more than 170 research papers, chapters and review articles; has multiple patents in the area of wound healing; and is a consultant for companies in the pharmaceutical and biotechnology industries.
Daniel J. Gibson is a doctoral candidate in biochemistry and molecular biology at UF. His research focuses on the role of growth factors, cytokines and proteases in wound healing in the skin and eye. He has a bachelor’s degree in mechanical engineering, which he uses to translate the products of his research into clinically applicable technologies; has multiple patents in the area of biochemical diagnostics; and consults on both diagnostics and drug delivery.
Iontophoresis is a well-known, noninvasive method that uses a small electric charge to deliver chemicals through the skin. However, according to Gregory Schultz, PhD, and Daniel Gibson, a professor and doctoral candidate, respectively, at the University of Florida, this method of delivery can have its drawbacks. Together with co-inventor, Sonal Sanjeev Tuli, MD, the team developed a method to iontophorese macromolecules into tissue such as the skin without causing damage; however, initial research focused on the eye.
Initial iontophoresis research began with the eye for a number of reasons. “We studied this delivery method on the cornea because not only is it a significant barrier, but also because the techniques used to deliver drugs into the skin, such as creams, penetrants and dimethyl sulfoxide, are toxic to the cornea,” noted Gibson.
The team began with the delivery of oligonucleotide-based drugs such as antisense oligonucleotides (ASOs) into the cornea. These DNA/RNA-based drugs serve as biomolecules to drive therapeutics in a targeted approach. “While we initially started with topical delivery, we found it was not getting into the cornea at all,” said Gibson.
Schultz agreed, “The passive diffusion methods for delivering these larger molecules was not delivering therapeutic amounts of the drugs.” Gibson likened the delivery of these macromolecules (1,000 g/mole) into the cornea to passing a tennis ball through a chain-link fence covered in Velcroa; the size is too large and the molecules adhere to the matrix or cells through normal biological reactions.
Schultz added that the affinity of macromolecules to water or lipids affects delivery. “Molecules that are applied topically and penetrate the skin well have a large hydrophobic component; but many drugs are hydrophilic, so they do not get across the lipid barrier of the stratum corneum,” he said.