Investigadores del MIT han desarrollado un parche portátil que aplica ondas de ultrasonido indoloras a la piel, creando pequeños canales a través de los cuales pueden pasar los medicamentos. Crédito: Cortesía de los investigadores.
Usando ondas de ultrasonido que impulsan las moléculas del fármaco hacia la piel, el parche podría usarse para tratar una variedad de afecciones de la piel.
The skin is an appealing route for drug delivery because it allows drugs to go directly to the site where they’re needed, which could be useful for wound healing, pain relief, or other medical and cosmetic applications. However, delivering drugs through the skin is difficult because the tough outer layer of the skin prevents most small molecules from passing through it.
In hopes of making 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 that drugs can pass through. This approach could lend itself to delivery of treatments for a variety of skin conditions, and could also be adapted to deliver hormones, muscle relaxants, and other drugs, the researchers say.
The patch is made of PDMS, a silicone-based polymer that can adhere to the skin without tape.
The patch is embedded with several disc-shaped piezoelectric transducers, pictured. Credit: Courtesy of the researchers
“The ease-of-use and high-repeatability offered by this system provides a game-changing alternative to patients and consumers suffering from skin conditions and premature skin aging,” says Canan Dagdeviren, an associate professor in MIT’s Media Lab and the senior author of the study. “Delivering drugs this way could offer less systemic toxicity and is more local, comfortable, and controllable.”
MIT research assistants Chia-Chen Yu and Aastha Shah are the lead authors of the paper, which was recently published in the journal Advanced Materials, as part of the journal’s “Rising Stars” series, which showcases 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 of Buffalo are also authors of the paper.
A boost from sound waves
The researchers began this project as an exploration of alternative ways to deliver drugs. Most drugs are delivered orally or intravenously, but the skin is a route that could offer much more targeted drug delivery for certain applications.
“The main benefit with skin is that you bypass the whole gastrointestinal tract. With oral delivery, you have to deliver a much larger dose in order to account for the loss that you would have in the gastric system,” Shah says. “This is a much more targeted, focused modality of drug delivery.”
Ultrasound exposure has been shown to enhance the skin’s permeability to small-molecule drugs, but most of the existing techniques for performing this kind of drug delivery require bulky equipment. The MIT team wanted to come up with a way to perform this kind of transdermal drug delivery with a lightweight, wearable patch, which could make it easier to use for a variety of applications.
El dispositivo que diseñaron consiste en un parche integrado con varios transductores piezoeléctricos en forma de disco, capaces de convertir corrientes eléctricas en energía mecánica. Cada disco está incrustado en una cavidad de polímero que contiene las moléculas del fármaco disueltas en una solución líquida. Cuando se aplica una corriente eléctrica a los elementos piezoeléctricos, generan ondas de presión en el fluido, creando burbujas que revientan contra la piel. Estas burbujas que revientan producen microchorros de líquido que pueden penetrar a través de la dura capa externa de la piel, el estrato córneo.
«Esto abre la puerta al uso de la vibración para mejorar la administración de fármacos. Varios parámetros dan como resultado la generación de diferentes tipos de patrones de forma de onda. Los aspectos mecánicos y biológicos de la administración de fármacos pueden mejorarse con este nuevo conjunto de herramientas», dice Karami.
El parche está hecho de PDMS, un polímero a base de silicona que puede adherirse a la piel sin cinta adhesiva. En este estudio, los investigadores probaron el dispositivo administrando una vitamina B llamada niacinamida, un ingrediente en muchos protectores solares y humectantes.
En pruebas con piel de cerdo, los investigadores demostraron que cuando administraban niacinamida con el parche de ultrasonido, la cantidad de fármaco que entraba en la piel era 26 veces mayor que la cantidad que podía pasar a través de la piel sin ayuda ultrasónica.
Los investigadores también compararon los resultados de su nuevo dispositivo con las microagujas, una técnica que a veces se usa para la administración transdérmica de medicamentos, que consiste en perforar la piel con agujas en miniatura. Los investigadores descubrieron que su parche podía administrar la misma cantidad de niacinamida en 30 minutos que podría administrarse con microagujas durante un período de seis horas.
Entrega a domicilio
Con la versión actual del dispositivo, los medicamentos pueden penetrar unos pocos milímetros en la piel, lo que hace que este enfoque sea potencialmente útil para los medicamentos que actúan localmente en la piel. Estos podrían incluir niacinamida o vitamina C, que se usa para tratar manchas de la edad u otras manchas oscuras en la piel, o medicamentos tópicos que se usan para tratar quemaduras.
Con otras modificaciones para aumentar la profundidad de penetración, esta técnica también podría usarse para medicamentos que necesitan llegar al torrente sanguíneo, como la cafeína,[{» attribute=»»>fentanyl, or lidocaine. Dagdeviren also envisions that this kind of patch could be useful for delivering hormones such as progesterone. In addition, the 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 on further optimizing the wearable patch, in hopes of testing it soon on human volunteers. They also plan to repeat the lab experiments they did in this study, with larger drug molecules.
“After we characterize the drug penetration profiles for much larger drugs, we would then see which candidates, like hormones or insulin, can be delivered using this technology, to provide a painless alternative for those who are currently bound to self-administer injections on a daily basis,” Shah says.
Reference: “A Conformable Ultrasound Patch for Cavitation-Enhanced Transdermal Cosmeceutical Delivery” by Chia-Chen Yu, Aastha Shah, Nikta Amiri, Colin Marcus, Md Osman Goni Nayeem, Amit Kumar Bhayadia, Amin Karami and Canan Dagdeviren, 19 March 2023, Advanced Materials.
DOI: 10.1002/adma.202300066
The research was funded by the National Science Foundation, a 3M Non-Tenured Faculty Award, the Sagol Weizmann-MIT Bridge Program, Texas Instruments, Inc., the MIT Media Lab Consortium, and a K. Lisa Yang Bionics Center Graduate Fellowship.