Ultrasound Beam Triggers ‘Nanodroplets' For Targeted Drug Delivery

Traditional methods of drug delivery are often inefficient and imprecise, dispersing medication throughout the body, including in areas where it’s not needed and may even be harmful. Achieving targeted delivery could significantly reduce the necessary dosage and minimize side effects. Scientists have now refined an emerging technique that achieves targeted drug delivery, making it safe and efficient for the first time and setting the stage for potential human trials.

Scientists at the University of Utah (Salt Lake City, UT, USA) have developed a technique that employs ultrasound waves to release drugs from nanocarriers at specific body sites. These nanocarriers are tiny, ranging from 470 to 550 nanometers in diameter, and consist of a hollow polymer shell. The shell’s polymers are designed with two ends: a 'hydrophilic' end that is compatible with water and faces outward, and a 'hydrophobic' end that repels water and faces inward. Enclosed within this shell is a core made up of hydrophobic perfluorocarbons, which are primarily composed of fluorine and carbon, mixed with a hydrophobic drug. This design prevents the cores from coalescing into a single droplet and forms a barrier against the immune system.

To trigger drug release, the team used ultrasound waves at frequencies of 300 or 900 kilohertz, which are beyond human hearing. The ultrasound beam can be precisely directed to target areas within the body that are just a few millimeters in size. It is believed that the ultrasound causes the perfluorocarbons within the nanocarriers to expand, stretching the droplet’s shell and increasing its permeability, allowing the drug to diffuse to the targeted organs, tissues, or cells. The effectiveness of the drug delivery was tested using the anesthetic propofol with different perfluorocarbons: perfluoropentane (PFP), decafluoropentane (DFP), and perfluorooctylbromide (PFOB).

The testing involved delivering ultrasound to the nanodroplets in vitro in 60 pulses of 100 milliseconds each over a minute. The results indicated that PFOB cores offered an optimal balance between droplet stability and delivery efficiency. For safety assessment, the researchers administered six doses of PFOB-based nanodroplets to a long-tailed macaque at weekly intervals, monitoring a series of blood biomarkers to track liver, kidney, and immune function. The study's results, which were published on June 19 in the journal Frontiers in Molecular Biosciences, confirmed that the nanodroplets were well tolerated and did not produce detectable side effects.

“Here we show a method to deliver drugs to specific areas of the body where they are needed. We do so using ultrasound waves, which trigger drug release from circulating nanocarriers when focused on the target,” said Matthew G Wilson, a graduate research assistant at the University of Utah, and the study’s first author. “We developed a method to produce stable nanocarriers repeatably, and identified ultrasound parameters that can activate them.”

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