Dr. Ajay K. Banga is Professor and Department Chair in the Department of Pharmaceutical Sciences at the College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA. He also holds an Endowed Chair in transdermal delivery systems.
The vast majority of transdermal patches on the market are the so-called passive diffusion systems where a moderately lipophilic drug diffuses into the lipid layers of the skin and is then able to partition out of skin into the blood for systemic absorption. Peptides and proteins, being hydrophilic macromolecules, are not able to diffuse into skin. Since many of the new products are protein-based and face challenges for delivery systems (e.g., frequent injections required due to short half-life and lack of oral bioavailability), considerable effort has been spent over the past several years to use physical technologies to enable their transdermal delivery. These technologies include, but are not limited to, iontophoresis, microporation, sonophoresis, and electroporation1.
Iontophoresis uses a small physiologically acceptable electric current to push similarly charged drug molecules into the skin. Several iontophoresis patches for drug delivery have been approved, and iontophoresis cosmetic patches to deliver anti-aging actives are also on the market. Iontophoresis has been found to be very effective in delivering large molecules, provided they are soluble in water (e.g., proteins). We have shown the delivery of macromolecules as large as 13 kDa using iontophoresis. Even larger molecules can be delivered by other technologies such as sonophoresis and microporation1. One popular microporation approach being investigated is the use of microneedles to create microscopic holes in the skin which are much smaller than those formed by an injection but still large enough to allow even the largest dissolved macromolecule to pass through. Cosmetic microneedle devices are already on the market and a microneedle-based flu vaccination product has recently been launched.
But while these delivery systems allow the delivery of hydrophilic macromolecules which will otherwise not enter the skin, they don’t necessarily deliver larger quantities and therefore the drug still needs to be potent to be a good candidate for delivery. This is generally not a problem for proteins and vaccines, with the possible exception of monoclonal antibodies, which tend to have larger dosage requirements. These physical technologies have also faced setbacks as some products were withdrawn from market after launch due to issues such as leakage or lack of adequate sales to sustain the product. Still, research continues and these technologies will have their place in the product portfolios, especially for niche markets where they meet a clear unmet therapeutic need.
What areas of research are the most promising to deliver hydrophilic macromolecules?