Abstract:

A feasibility study of using high amplitude ultrasound to deliver large molecules transdermally was undertaken. Ultrasound (20 kHz) of intensity in the range between 2 to 50 W/cm[sup 2] was used to increase the permeability of skin in vitro to poly-l-lysines as models of drug molecules. When 20 kHz, 5% duty cycle ultrasound at the spatial average and pulse average intensity I[inf SAPA]=19 W/cm[sup 2] was applied for 10 min the skin permeability was calculated to be 0.5(plus or minus)0.2 cm/h and 8.5(plus or minus)4.2 cm/h, respectively, for poly-l-lysine-FITC (51 kDa) and octa-l-lysine-FITC (2.5 kDa). Without application of ultrasound the skin permeability of the above-mentioned molecules was essentially zero. A transdermal flux enhancement occurred during the process reported here was much higher than that due to sonophoresis (I[inf SAPA]<2 W/cm[sup 2]) as reported in literature (Mitragotri et al., 1995). Reported here are experimental results from transdermal flux kinetis, and confocal microscopic cross sectional and optical images suggest the formation of pores in the stratum corneum whose size varies with skin samples and may be in the range of 1--100 (mu)m. The confocal images also suggest the formation of micron-size pathways in epidermis during ultrasound exposure.