Effective drug release from safe ultrasound-triggered nanocarriers

Abstract

Selective delivery of medication into specified tissue targets would realize the promise of personalized medicine with minimal side effects. Such an approach could be particularly transformative for patients with brain disorders, in whom drugs could be released in the impaired brain circuits at high concentration while sparing other brain regions and organs. Focused ultrasound provides noninvasive and practical means to release drugs from nanocarriers selectively at its target. However, which nanoparticle formulations provide safe and effective release and under which ultrasound parameters has been unclear. To expedite regulatory approval, we tested release effectiveness from nanocarriers filled with perfluorocarbon cores of relatively high boiling points (up to 142°C). We confirmed the safety of these nanocarriers in non-human primates. Crucially, we found that these safe, high-boiling-point nanocarriers can be used for effective release so long as they are activated by ultrasound of frequencies lower than those used previously (300 kHz). This study informs the formulation and release parameters for safe and effective drug delivery in specific parts of the body or brain regions.Abstract FigureDrugs can be effectively released from ultrasound-sensitive nanoparticles filled with safe, high-boiling point cores so long as they are activated by low-frequency ultrasound.