High-frequency ultrasonic atomization for drug delivery to rodent animal models - optimal particle size for lung inhalation of difluoromethyl ornithine.

A high-(8-MHz) and a low-(1.7-MHz) frequency ultrasonic transducer were compared for delivering aerosols to mouse lung. The aerosol concentration (mass of dry particles/volume of air) rose nonlinearly with solution concentration of difluoromethyl ornithine for both transducers. The particle size was linear with the cube root of the solution concentration, and the slope of the low-frequency transducer was 8 times greater than that of the high-frequency transducer. The deposition fraction assessed by the assayed mass in the lung relative to the calculated inhaled mass was found to decline exponentially with particle size. The lower-frequency transducer provided a higher dose despite a lower deposition fraction, but the high-frequency transducer was more efficient and provides a more selective deposition in the lower respiratory tract while operating with significantly less demands on aerosol drying.