My Alzheimer's Journey
Part 87 - History of Ultrasound Enhanced Drug Delivery
I want to take a moment to remember Jesse Jackson, who died early this morning. He was a United States civil rights icon. His tireless work in racial and economic justice who be felt for eternity.
Yesterday, I presented an overview of the Focused Ultrasound Foundation. The Foundation provides funding and leadership for research projects with a “goal of making focused ultrasound available to patients in the shortest time possible.”
Today, I want to write about the history of ultrasound enhanced drug delivery (also known as ultrasound mediated drug delivery).
At its core, ultrasound enhanced drug delivery is based on the mechanical properties of ultrasound (US), which makes the delivery of therapeutic drugs through biological barriers such as cell membranes and the particularly hard to cross blood–brain barrier (BBB). US refers to any sound waves with frequencies greater than 20kHz. Diagnostic ultrasound typically uses frequencies between 2 and 20 million Hertz (Megahertz - MHz).
US is used in many home devices today. Plug-in bug and rodent repellants, automatic vacuum cleaners, and ultrasonic jewelry cleaners, are a few examples. For comparison purposes, ultrasonic bug repellants emit sound waves in the 20KHZ-60KHZ frequency range. There is a massive difference in energy concentration and spatial resolution between the US used in a bug and rodent repellant and a focused US used in drug delivery. Same basic technology, though.
The actual process of ultrasound enhanced drug delivery, are these three steps:
US waves induce pressure alterations in tissue
creating a phenomenon known as cavitation, or MB
finally, an implosion within a fluidic environment
At that point, specific acoustic phenomena including microstreaming and shockwaves are created. This action leads to transient cellular openings or disruption of intercellular junctions. In simple terms, this actions allows substances, fluids, or ions to pass through a barrier, such as cell membranes, blood vessels, or even the BBB.
In the 1980s, MBs (biocompatible bodies filled with gas) were used as an ultrasonic contrast agent (UCA) for diagnostic purposes. Scientists discovered that when the gas core of the MBs interacted with US waves, the MBs would expand and contract rapidly in response to the pressure changes induced by the US wave. Suddenly, the MBs could be controlled and directed to a certain degree.
The Focused Ultrasound Foundation was founded in 2006. Some of the founders of the Foundation, were neurologists and medical researchers. They saw the potential of US. A vision quickly became a passion.
The Foundation prioritized research of the development of noninvasive, US technology for brain diseases. In 2009, the Foundation identified using focused ultrasound to treat movement disorders (such as Parkinson’s disease and essential tremor) as a top priority.
Fast-forward to 2022, German landrace pigs received a 30-min infusion of doxorubicin (cancer drug). The infusion contained thermosensitive liposomes (in basic laymen’s terms, thermosensitive liposomes are MBs.) The pigs' biceps were treated locally in two separate target areas with mild hyperthermia using magnetic resonance guided by focused ultrasound. This was the first time US had been used for drug therapy delivery.
The interaction between the US and these MBs offered “a synergy as it amplified the mechanical effects of the US, thereby enhancing the extravasation of therapeutic molecules through biological barriers in a process termed sonoporation.”
US enhanced drug delivery holds tremendous potential in oncology, neurology, cardiology, and gene therapy. In neurology, US offers innovative ways to deliver therapeutic agents across the BBB.
Tomorrow, I will write about the exciting studies and trials currently underway using US focused drug delivery for Alzheimer’s disease.
I did most of the research for this article while receiving my tenth Lecanemab infusion at Duke Health this morning. I kept thinking of the low percentage of the drug that is actually reaching my brain. Ultrasound enhanced drug delivery would be so much better.
Thank you for reading my articles. I certainly hope you find them informative and helpful no matter what role you have with this horrible disease. I also deeply appreciate your financial support.
Sources:
Thermosensitive liposomal drug delivery systems: state of the art review