SONOPHORESIS EFFECT ON THE PERMEATION OF METRONIDAZOLE USING 3D SKIN EQUIVALENT

Transdermal drug delivery is highly advantageous method for drug administration, yet the compact structure of stratum corneum is an effective barrier which limited the use of this route to very few drug molecules. Ultrasound enhances the permeation through the skin by altering this barrier function in a phenomenon named sonophoresis. This study aimed to evaluate the effect of variable ultrasonic conditions on the permeation of Metronidazole (ML). This involved validating the applicability of utilizing a three dimensional skin equivalent as human skin models for sonophoresis studies. A Franz diffusion cell was used to study the effect of therapeutic ultrasound at 1 MHz and power ultrasound at 20 KHz on the permeation of Metronidazole across the 3D skin equivalent EpiDerm™. HPLC methods were used for the determination of the concentration of Metronidazole in the receiving compartment. Utilizing therapeutic ultrasound at 1 MHz frequency has enhanced the permeation of Metronidazole through the EpiDerm™, as about double the permeation of the ML was obtained with no apparent damage to the membrane. The results indicated significant permeation enhancement with low frequency sonophoresis at 20 KHz frequency treatments through EpiDerm™ skin equivalent. Up to five fold enhancement was measured with the permeation of investigated molecules through EpiDerm™. The mechanism of action observed seemed highly dependent on the ultrasonic conditions.