Transdermal delivery of poly-l-lysine by sonomacroporation

A feasibility study of using high-amplitude ultrasound (US) to deliver large molecules transdermally was undertaken. US (20 kHz) of intensity in the range between 2 to 50 W/cm(2) was used to increase the permeability of skin in vitro to large size molecules. For example, when 20-kHz, 5% duty cycle US at the spatial average and pulse-average intensity I(SAPA) = 19 W/cm(2) was applied for 10 min and the distance between the US source and the surface of a skin specimen was 2 mm, the skin permeability was calculated to be 0.5 +/- 0.2 cm/h and 8.5 +/- 4.2 cm/h, respectively, for poly l-lysine-fluorescein isothiocyanate (FITC) (51 kDa) and octa-1-lysine-FITC (2.5 kDa). Without application of US, the skin permeability of the above-mentioned molecules would be essentially zero. A transdermal flux enhancement occurring during the process reported here was much higher than that due to sonophoresis (I(SAPA) < 2 W/cm(2)) as reported in the literature. For comparison, for example, the skin permeability for delivering erythropoeitin (48 kDa) and insulin (6 kDa) reached 9.8 x 10(-6) and 3.3 x10(-3) cm/h, respectively, by using sonophoresis for 1 h US exposure. Experimental results from transdermal flux kinetics, and confocal microscopic cross-sectional and optical images, suggested that the formation of pores in the stratum corneum, whose size varies with skin samples, may be in the range of 1 to 100 microm. The confocal images also suggest the formation of microm-size pathways in epidermis during US exposure.