Feasibility of using focused acoustic vortex for enhancing transdermal delivery

Transdermal delivery is a convenient and noninvasive route for drug administration across several medical applications. However, its efficacy is significantly hindered by the barrier function of the skin stratum corneum. Previous studies have investigated various ultrasound-based configurations for noninvasively enhancing transdermal drug penetration; however, the requirements for prolonged sonication, high energy levels, and microbubble cavitation have raised safety concerns. This study proposed a 1-MHz focused acoustic vortex (FAV) approach that overcomes these limitations. The FAV approach applies phase dislocations to generate sound waves that travel in a spiral motion around the beam axis, producing localized vortical flow with high shear stress. The results indicate that FAV could instantaneously induce vortical flow with a diameter of 2.4 mm that stabilizes within 10 s. Peak streaming velocity, measured at 1.6 ± 0.4 mm/s, was achieved at acoustic pressure of 1 MPa and a duty cycle of 60 %. Under these parameters, sonication for 3 min significantly enhanced the penetration depths of Evans blue (EB, 960 Da, hydrophilic) dye and fluorescein isothiocyanate-labeled dextran (4000, and 150 000 Da, hydrophilic) in porcine skins, increasing them 3.3-fold and 2.1-fold, respectively, compared with conventional focused ultrasound. Moreover, FAV also doubled the penetration depth of EB in rat skins in comparison to regular focused ultrasound (1 MPa, duty cycle of 60 %, 3 min sonication duration) without inducing temperature elevation and inertial cavitation in vivo. This technique enables the permeabilization of the stratum corneum, improving drug penetration of transdermal delivery without the adverse effects associated with cavitation in microbubble methods.