High Frequency Capillary Wave Enabled Ultra-small Droplets for Inhaled Drug Delivery

Abstract

Benefiting from localization, targeting and rapid response, inhaled drug delivery has become an indispensable method for lung diseases treating. However, the efficacy of drug delivery is often compromised by the physical characteristics of the aerosol produced by current nebulization methods: large droplet size distributions, which is deposited in the upper airways. In this study, an appropriate size distributions, portable, low energy and low-cost approach is introduced to nebulize drug using capillary wave breakup induced by gigahertz (GHz) acoustic waves. A delicately designed miniaturized nebulizer is developed by integrating the GHz bulk acoustic resonator with semi-opened microchannel to nebulize droplets of optimal size for pulmonary inhalation, with size distributions that 96% are smaller than 5 μm at low power, that surpass existing methods. In addition, this technique facilitates the nebulization of liquids with viscosities up to 5000 cP. Low-flux lung models achieve 88% drug delivery efficiency. Murine in vivo tests demonstrate the efficacy of proposed nebulizer in lung-targeted delivery via autonomous inhalation, attributed to optimized droplet size and flux. The tunable sizes, broad range of nebulization viscosities, suitable fluxes, pumpless operation and low cost highlight the potential for autonomous lung drug delivery and combination therapy targeting both small airways and alveoli.