Hydrogel with ultrasound activation enables sustained release of active ingredients

Researchers at Michigan Medicine have developed a composite hydrogel that can achieve sustained, consistent drug release using ultrasound as a trigger.

The team behind the breakthrough believes it could revolutionize drug delivery for various medical applications where consistent drug levels are critical for optimal therapeutic outcomes.

The resulting article, “Acoustically Responsive Scaffolds: Unraveling Release Kinetics and Mechanisms for Sustainable, Steady Drug Delivery,” appears in the October 2024 issue of Controlled Release Journal.

The composite, called an acoustically responsive scaffold, uses a fibrin hydrogel matrix.

When exposed to ultrasound, an emulsion embedded in the hydrogel evaporates into bubbles and releases the encapsulated active ingredient.

There are drug delivery devices, such as osmotic pumps, that enable zero-order release, i.e. constant release over time.

However, these methods often have limitations that could be overcome with this fibrin hydrogel.

“A key advantage of our system is the use of fibrin, a biocompatible material that breaks down naturally in the body,” said Haijun Xiao, Ph.D., research associate at the Michigan Medicine Ultrasound Laboratory and lead author of the paper.

“This eliminates the need for surgical removal of the drug delivery device after treatment, as is sometimes required with other implantable systems.”

The ability to control the ultrasound allows for zero-order sustained release. One process allows for the delivery of a constant level of drug over an extended period of time.

“This publication can improve the effectiveness of treatment and minimize side effects associated with fluctuating drug concentrations,” Xiao said.

Xiao developed step-by-step equations to specifically describe the multiphase release behavior of the acoustically responsive scaffolds, which includes an initial rapid release upon ultrasonic activation followed by a sustained zero-order release phase.

These equations provide a new framework for the development and optimization of ultrasound-triggered drug delivery systems.

The Michigan Medicine Ultrasound Laboratory has already pioneered the use of these scaffolds to stimulate blood vessel growth.

Applying this technology to drug delivery offers several advantages: on-demand drug release, personalized treatment regimens and non-invasive dose adjustments.

“Having a mathematical model that accurately describes the release process from the ARS is critical to ultimately personalizing treatment,” said Mario L. Fabiilli, Ph.D., principal investigator in the ultrasound laboratory and senior author of the paper.

“In the future, these equations will enable us to non-invasively tailor the drug dosage precisely to the individual needs of the patient.”

The research team is currently exploring the development of acoustically responsive scaffolds capable of delivering multiple growth factors sequentially, potentially creating the opportunity for more sophisticated applications in tissue engineering and regenerative medicine.