Nanobubble Transport through Membrane Insert and Agarose Gel

Nanobubbles are gaseous vesicles under 1 micrometer in size, widely used in medical imaging and drug delivery. Their compressibility enhances ultrasound imaging, while their small size allows for extravasation into tumors via the enhanced permeation and retention effect. However, drug delivery remains challenging due to high interstitial pressure within tumors, which limits penetration to the core. To address this, nanobubbles can serve as drug delivery devices, with controlled release triggered by focused ultrasound. Understanding their transport behavior is crucial, particularly in the tumor microenvironment. This study investigates the effect of ultrasound and presence of shear on the permeation of nanobubbles through the tumor interstitium. Rhodamine-loaded nanobubbles, mimicking drug-loaded delivery device, were introduced into a membrane insert system containing an agarose-gel layer simulating the tumor interstitium. Nanobubble concentration in the receiver well was monitored via fluorescence intensity, assessing transport efficiency under different conditions. Comparisons with non-echogenic fluorescent dextrans provided insights into distinct nanoparticle behaviors. Results showed that ultrasound significantly enhanced nanobubble permeation, whereas the presence of shear primarily benefited dextran transport. These findings highlight the unique responsiveness of nanobubbles to ultrasound, offering a promising strategy for improving drug delivery in solid tumors.