Researchers from Japan may have made great strides in the advancement of drug delivery, by finding a way to make the skin “thinner,” making it easier for drugs to pass through and enter the bloodstream.
Our skin provides us with an impermeable barrier to the environment. This is good, because it means that our skin is waterproof, which protects us from dehydration. Skin also acts as a natural barrier to pathogens, such as bacteria and viruses.
In order to administer drugs, the skin needs to be bypassed. This is most commonly done by injection, which disrupts the skin barrier, leaving us vulnerable to infection. It is also often painful.
Another method of delivering drugs is orally, but enzymatic digestion of drugs and potential toxicity are risk factors. In order to deliver a drug through the skin without damaging the skin barrier function, the skin has to be made “leaky.”
The outer layer of the skin is made up of dead cells, which are glued together by specialized lipids and proteins. These cells form a multi-layered structure called the stratum corneum.
Very few drugs can cross the stratum corneum by passive diffusion. To make skin leaky, the structures between the cells in the stratum corneum have to be disrupted, without damaging the cells or leaving it vulnerable to infection. Drugs can then enter the body through the skin – transdermal delivery – and enter the bloodstream or the immune system.
New methods to achieve this are therefore of great interest to scientists and pharmaceutical companies who want to develop drugs for transdermal delivery.
Scientists in Japan have been working on a different method to disrupt the impermeable stratum corneum using treatment with atmospheric microplasma.
Plasma is the fourth state of matter, the others being solid, liquid, and gas. Plasma can be produced by partial ionization of a gas.
Plasma is commonly used for the sterilization and treatment of surfaces in industrial applications. When atmospheric air is used for this process, the resultant plasma is called atmospheric plasma. When plasma is generated in a very small space, covering only micrometer distances, it is termed microplasma.
Researchers from Shizuoka University in Japan compared the effect of plasma treatment using conductive and non-conductive materials on the stratum corneum.
The team presented their findings at the 63rd Annual Symposium and Exhibition of the American Vacuum Society (AVS), held in Nashville, TN.
For this study, they used the skin from mini pigs, as pig skin most closely resembles that of humans.
Treatment using a conductive material resulted in significant damage to the skin by the plasma jet, with small holes and burnt areas. But treatment on a non-conductive material using atmospheric microplasma showed no damaging effect on the skin.
Importantly, the microplasma treatment resulted in increased permeability, which was measured using a specialized type of spectroscopy and a dye test.
The skin is normally impermeable to dyes, but microplasma treatment resulted in leaky skin, allowing the dye to penetrate the stratum corneum. This indicates that drugs could also permeate the stratum corneum after microplasma treatment and be absorbed by the skin.
A combination of Attenuated Total Reflectance (ATR) and Fourier Transformed Infrared (FTIR) spectroscopy (ATR-FTIR) was used to test the structure of the skin after microplasma treatment.
This technique indicated that there was a change to the chemical structure of the skin, but that it was not damaged.
The data presented indicate that microplasma treatment could be used to improve transdermal delivery of drugs.
The authors did however note in their recent publication in the journal Biofabrication that “the microplasma irradiation to living bodies (including humans) and the effect of the applied voltage waveform need to be confirmed in future clinical studies.”
This work shows that innovative solutions are needed to address the problem of transdermal delivery of drugs.
“Placement of skin on the conductive material caused burned spots on the skin by the plasma jet, while treatment of the skin by microplasma showed little physical damage.”
Study co-author Dr. Marius Blajan, Shizuoka University