T-00069: Method for Simultaneous Delivery of Multiple Drugs Through Skin

Inventors: Omathanu Perumal, Preety Sahdev, Vamsi Venuganti, Radhey Kaushik
Article by Lance Nixon

South Dakota State University research using an innovative strategy for delivering gene-based medications through the skin reduced the volume of skin tumors by 60 percent in mice.

Associate professor Omathanu Perumal in SDSU’s Department of Pharmaceutical Sciences is leading the research. His team includes Vamsi Venuganti, a graduate student working with Perumal, distinguished professor Chandradhar Dwivedi, head of the Department of Pharmaceutical Sciences, and associate professor Radhey Kaushik of SDSU’s Department of Biology and Microbiology.

The medication they used in the experiment is a technology called “antisense therapy” that interrupts the cancer cells’ messaging in what Perumal calls “biological jamming” of signals. That is, the medication interrupts the way cancer cells’ DNA  produces a protein that forms the skin cancer.

What is innovative about the SDSU work is a new approach that combines techniques for delivering medications through the skin and modifying the DNA-based medicine.

Delivering medications through skin is not a new concept.  Skin is easily accessible and, with a surface area of about 20 square feet, is the largest organ of the human body.

 A motion sickness drug delivered through the skin via a patch came into use in the early 1980s, and nicotine replacement therapy with patches has also been successful in the years since then. But there are still only about 12 to 14 drugs that can be delivered through the skin, Perumal said, and those tend to be potent, lipid-soluble, low-dose small- molecule drugs.

“The difficulty is that the skin is also one of the most highly impermeable membranes of the human body. It’s designed to protect the other organs of the body against external agents.”

Since the function of skin is to act as a barrier, it will naturally resist entry of any foreign material into the body, including any drugs.  However, altering the skin for a period of time could allow entry of the drug through skin in a safe manner. Some of the methods that are known to alter skin are small electrical current, ultrasound, and microneedles.

Another way to deliver drug through skin is to alter the drug.  This is particularly difficult for some of the new generation of drug currently under development such as DNA-based medicines.

The difficulty for the therapy, Perumal said, is that DNA-based medicines— the kind that ‘jams’ cancer cells’ messages, for example — are large molecules with a negative charge. That is a problem because most of the biological membranes of the body including skin are negatively charged, which poses a challenge in getting these drugs past skin and also across the cancer cells because they repel each other.

“Our goal is to modify the charge of the DNA and then get it into the skin,” Perumal said. “We take DNA, which is negatively charged, and we join it with a polymer which is positively charged to form a complex.”

The advantages of this complex are that it is more stable than the DNA-based medicine alone; it is positively charged and can be taken up easily by negatively charged cells.

In addition to creating positively charged DNA-based medicine, which allows negatively charged skin to attract medicine, a technology called iontophoresis is used to push the charged complex via two processes called as electrorepulsion and electroosmosis.  Iontophoresis does this by generating an electrical field with a small electrical current (similar to the current supplied by a watch batter), which allows the positively charged complex to penetrate much better into the skin.

“There are a couple of iontophoretic patches already in the market for small drugs used for numbing the skin and for pain management, but we have shown that this technology can also be used for delivering large molecules such as DNA,” Perumal said.

The Skin Cancer Foundation and the South Dakota 2010 Initiative are funding the research. As the work proceeds, Perumal said, SDSU will also explore the same combination strategy for delivering drugs to treat melanoma, a very serious form of skin cancer, as well as other skin conditions such as psoriasis, and also for delivering vaccines through skin.