Development of Nanobubbles for the Hights of Ultrasound-mediated Delivery

Abstract

Ultrasound-responsive drug delivery systems (DDS) enable precise delivery control using external physical stimuli, and their application research is advancing in the field of nucleic acid therapeutics. In particular, DDS based on bubble formulations derived from ultrasound contrast agents has attracted attention as a foundational technology for integrated theranostics, combining low invasiveness with irradiation site specificity. We have developed ultrasound-responsive nanobubbles (NBs) using PEG-modified liposomes and demonstrated their utility as a delivery platform applicable to various nucleic acid therapeutics. This review outlines our previous research achievements, including NBs design and functionalization strategies, their applications to nucleic acid therapeutics, and the production of homogeneous formulations using microfluidic technology. Furthermore, we provide an overview of integrated development trends for devices and bubble formulations that contribute to realizing theranostics and optimizing irradiation conditions according to disease and tissue characteristics. We also indicate directions for improving the performance and future advancement of ultrasound-mediated DDS.