Harnessing the power of sound waves for advances in drug delivery

Harnessing the power of sound waves for advances in drug delivery
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Pioneering new research is harnessing the power of sound waves to deliver drugs – demonstrating how high-frequency sound could revolutionise the field of ultrasound-driven chemistry.

Researchers at RMIT University in Melbourne, Australia, have revealed how high-frequency sound waves can be used to deliver drugs to the lungs for painless, needle-free vaccinations, as well as using them to build new materials and make smart nanoparticles.

Sound waves have been part of science and medicine for decades, for example, ultrasound was first used for clinical imaging in 1942 and for driving chemical reactions in the 1980s. However, technologies have always relied on low frequencies.

The new research, published in Advanced Science, has unveiled the unusual effects of high-frequency sound waves on materials and cells. Lead researcher Distinguished Professor Leslie Yeo says that the research challenges long-held physics theories, opening up a new field of “high-frequency excitation” in parallel to sonochemistry.

“The classical theories established since the mid-1800s don’t always explain the strange and sometimes contradictory behaviour we see – we’re pushing the boundaries of our understanding,” he said.

Sonic waves

Yeo and his team have spent over a decade researching the interaction of sound waves at frequencies above 10 MHz with different materials but are only now starting to understand the range of strange phenomena they observe in the lab.

Ultrasound has long been used at low frequencies – around 10 kHz to 3 MHz – to drive chemical reactions, a field known as “sonochemistry”. At these low frequencies, sonochemical reactions are driven by the violent implosion of air bubbles, a process known as cavitation. This results in huge pressures and ultra-high temperatures.

The researchers, including Dr Amgad Rezk, Dr Heba Ahmed and Dr Shwathy Ramesan, have now discovered that if high-frequency sound waves are used instead, these reactions change completely.

The team have been generating high-frequency sound waves on a microchip to precisely manipulate fluids or materials.

Yeo said: “When we couple high-frequency sound waves into fluids, materials, and cells, the effects are extraordinary. We’ve harnessed the power of these sound waves to develop innovative biomedical technologies and to synthesise advanced materials. But our discoveries have also changed our fundamental understanding of ultrasound-driven chemistry – and revealed how little we really know.

“Trying to explain the science of what we see and then applying that to solve practical problems is a big and exciting challenge.”

When high-frequency sound waves were transmitted into various materials and cells, the researchers saw behaviour that had never been observed with low-frequency ultrasound.

Yeo added: “We’ve seen self-ordering molecules that seem to orient themselves in the crystal along the direction of the sound waves. The sound wavelengths involved can be over 100,000 times larger than an individual molecule, so it’s incredibly puzzling how something so tiny can be precisely manipulated with something so big.

“It’s like driving a truck through a random scattering of Lego bricks, then finding those pieces stack nicely on top of each other – it shouldn’t happen!”

Revolutionising drug delivery

When using high-frequency sound waves, molecules and cells stay mostly intact, unlike when using low-frequency sound waves – meaning high-frequency waves can be used in biomedical devices to manipulate biomolecules and cells. This is the basis for the various drug delivery technologies patented by the RMIT research team.

One of these devices is a lightweight and portable advanced nebuliser that can precisely deliver large molecules such as DNA and antibodies, which could lead to painless, needle-free vaccinations and treatments.

The nebuliser uses high-frequency sound waves to excite the surface of the fluid or drug, generating a fine mist that can deliver larger biological molecules directly to the lungs, and can be used to encapsulate a drug in protective polymer nanoparticles in a one-step process.

The researchers have also shown how irradiating cells with the high-frequency sound waves allows therapeutic molecules to be inserted into the cells without damage, a technique that can be used in emerging cell-based therapies.

As well as using high-frequency sound waves to drive crystallisation for the sustainable production of metal-organic frameworks, the next steps for the RMIT team are focused on scaling up the technology.

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