Effects of low-intensity focused ultrasound on the mouse submandibular gland

Ultrasound is expected to make a considerable contribution to drug delivery systems (DDSs). We tested the hypothesis that low-intensity focused ultrasound (LIFU) increases vessel permeability in the mouse submandibular gland without causing parenchymal damage. In a preliminary study, LIFU at 3 W/cm2 with a 50% duty cycle for 2 minutes did not cause histologic damage. We therefore applied LIFU to mouse submandibular gland at these conditions before and after injecting horseradish peroxidase. Single labeling laser scanning confocal microscopy revealed positive horseradish peroxidase staining around the excretory ducts in the mucous-producing part of the gland, but absence of staining in control glands. Immunostaining for fibrinogen was positive in the same region. Fibrinogen is an intravascular protein that does not pass through intact vessels. These findings suggest that LIFU increases vessel permeability and disruption without destruction. It is anticipated that this process will be useful in establishing a DDS that uses LIFU.