The skin is an attractive route for drug delivery because it allows drugs to go directly to where they are needed, which could be useful for wound healing, pain relief, or other medical and cosmetic applications. However, drug delivery through the skin is difficult because the tough outer layer of the skin prevents most small molecules from getting through.
Hoping to make it easier to deliver drugs through the skin, MIT researchers have developed a wearable patch that applies painless ultrasonic waves to the skin, creating tiny channels through which drugs can pass. This approach could lend itself to delivering treatments for a variety of skin conditions and could also be adapted to deliver hormones, muscle relaxants and other drugs, the researchers say.
“The ease of use and high repeatability offered by this system provides an innovative alternative for patients and consumers suffering from skin conditions and premature skin aging,” says Canan Dagdeviren, associate professor at the MIT Media Lab and author major. of the study. “Administering drugs this way may offer less systemic toxicity and is more local, convenient, and controllable.”
MIT research assistants Chia-Chen Yu and Aastha Shah are the lead authors of the paper, which appears in Advanced Materials, as part of the magazine’s “Rising Stars” series, showcasing the outstanding work of researchers in the early stages of their independent careers. Other MIT authors include research assistant Colin Marcus and postdoc Md Osman Goni Nayeem. Nikta Amiri, Amit Kumar Bhayadia and Amin Karami of the University at Buffalo are also authors of the paper.
An impulse of sound waves
The researchers began this project as an exploration of alternative ways to deliver drugs. Most drugs are administered orally or intravenously, but the skin is one route that could offer much more targeted drug delivery for certain applications.
“The main benefit with the skin is that it bypasses the entire GI tract. With oral administration, you have to give a much higher dose to make up for the loss you would have in the gastric system,” Shah says. “This is a much more specific and focused modality of drug delivery.”
Ultrasound exposure has been shown to improve skin permeability to small molecule drugs, but most existing techniques for performing this type of drug delivery require bulky equipment. The MIT team wanted to devise a way to perform this type of transdermal drug delivery with a lightweight, portable patch, which could make it easier to use for a variety of applications.
The device they designed consists of a patch embedded with several disc-shaped piezoelectric transducers, which can convert electrical currents into mechanical energy. Each disk is embedded in a polymeric cavity that contains the drug molecules dissolved in a liquid solution. When an electrical current is applied to the piezoelectric elements, they generate pressure waves in the fluid, creating bubbles that burst against the skin. These bursting bubbles produce micro-jets of fluid that can penetrate through the tough outer layer of the skin, the stratum corneum.
“These works open the door to the use of vibrations to improve drug delivery. There are several parameters that result in the generation of different types of waveform patterns. This new set of tools can improve both the mechanical and biological aspects of drug delivery,” says Karami.
The patch is made of PDMS, a silicone-based polymer that can adhere to the skin without tape. In this study, the researchers tested the device by administering a B vitamin called niacinamide, an ingredient in many sunscreens and moisturizers.
In tests on pig skin, the researchers showed that when niacinamide was administered with the ultrasound patch, the amount of drug that penetrated the skin was 26 times greater than the amount that could pass through the skin without ultrasound assistance.
The researchers also compared the results of their new device with microneedling, a technique sometimes used for transdermal drug delivery that involves puncturing the skin with miniature needles. The researchers found that their patch could deliver the same amount of niacinamide in 30 minutes that could be delivered with microneedles over a six-hour period.
local delivery
With the current version of the device, drugs can penetrate a few millimeters into the skin, making this approach potentially useful for drugs that act locally within the skin. These could include niacinamide or vitamin C, used to treat age spots or other dark spots on the skin, or topical medications used to heal burns.
With further modifications to increase depth of penetration, this technique could also be used for drugs that need to reach the bloodstream, such as caffeine, fentanyl, or lidocaine. Dagdeviren also envisions that this type of patch could be useful for delivering hormones such as progesterone. In addition, researchers are now exploring the possibility of implanting similar devices inside the body to deliver drugs to treat cancer or other diseases.
The researchers are also working to further optimize the wearable patch, hoping to test it on human volunteers soon. They also plan to repeat the lab experiments they did in this study, with larger drug molecules.
“After characterizing the drug penetration profiles for much larger drugs, we would see which candidates, such as hormones or insulin, can be delivered using this technology, to provide a painless alternative for those currently forced to self-administer injections on a daily basis. Shah says.
The research was funded by the National Science Foundation, a 3M Non-Tenuous Faculty Award, the Weizmann-MIT Sagol Bridge Program, Texas Instruments, Inc., the MIT Media Laboratory Consortium, and a Graduate Grant from the Center for Bionics K. Lisa Yang.
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