Using ultrasound waves, engineers at Massachusetts Institute of Technology (MIT) in Cambridge, CA, US have found a way to enhance the permeability of skin to drugs, making transdermal drug delivery more efficient.
The researchers say this technology could pave the way for non-invasive drug delivery or needle-free vaccinations.
Carl Schoellhammer, an MIT graduate student in chemical engineering and one of the lead authors of a recent paper published in the Journal of Controlled Release, says: ‘This could be used for topical drugs such as steroids — cortisol, for example — systemic drugs and proteins such as insulin, as well as antigens for vaccination, among many other things.’
Ultrasound can increase skin permeability by lightly wearing away the top layer of the skin, an effect that is transient and pain-free.
The researchers found that applying two separate beams of ultrasound waves — one of low frequency and one of high frequency — can uniformly boost permeability across a region of skin more rapidly than using a single beam.
When ultrasound waves travel through a fluid, they create tiny bubbles that move chaotically. Once the bubbles reach a certain size, they become unstable and implode. Surrounding fluid rushes into the empty space, generating high-speed “microjets” of fluid that create microscopic abrasions on the skin. In this case, the fluid could be water or a liquid containing the drug to be delivered.
In recent years, researchers working to enhance transdermal drug delivery have focused on low-frequency ultrasound, because the high-frequency waves do not have enough energy to make the bubbles pop. However, those systems usually produce abrasions in scattered, random spots across the treated area.
In the new study, the MIT team found that combining high and low frequencies offers better results. The high-frequency ultrasound waves generate additional bubbles, which are popped by the low-frequency waves. The high-frequency ultrasound waves also limit the lateral movement of the bubbles, keeping them contained in the desired treatment area and creating more uniform abrasion, says Schoellhammer.
The researchers tested their new approach using pig skin and found that it boosted permeability much more than a single-frequency system. First, they delivered the ultrasound waves, then applied either glucose or inulin (a carbohydrate) to the treated skin. Glucose was absorbed 10 times better, and inulin four times better.
‘We think we can increase the enhancement of delivery even more by tweaking a few other things,’ Schoellhammer says.
Such a system could be used to deliver any type of drug that is currently given by capsule, potentially increasing the dosage that can be administered. It could also be used to deliver drugs for skin conditions such as acne or psoriasis, or to enhance the activity of transdermal patches already in use, such as nicotine patches.
Ultrasound transdermal drug delivery could also offer a non-invasive way for diabetics to control their blood sugar levels, through short- or long-term delivery of insulin, the researchers say.
Following ultrasound treatment, improved permeability can last up to 24 hours, allowing for delivery of insulin or other drugs over an extended period of time.
Such devices also hold potential for administering vaccines, according to the researchers. It has already been shown that injections into the skin can induce the type of immune response necessary for immunisation, so vaccination by skin patch could be a needle-free, pain-free way to deliver vaccines. This would be especially beneficial in developing countries, since the training required to administer such patches would be less intensive than that needed to give injections.
Groups led by Daniel Blankschtein, the Herman P Meissner ’29 Professor of Chemical engineering at MIT and Robert Langer, the David H Koch Institute Professor at MIT groups, and senior authors of the paper, are now pursuing this line of research.
They are also working on a prototype for a handheld ultrasound device, and on ways to boost skin permeability even more. Safety tests in animals would be needed before human tests can begin.
