Transdermal drug delivery using low-frequency sonophoresis

Area of Science:

• Pharmacology
• Biophysics
• Materials Science

Background:

• Therapeutic ultrasound (1-3 MHz) improves transdermal drug transport, but with limited efficacy (enhancement factor < 10).
• Developing novel methods to significantly enhance transdermal drug delivery is crucial for effective topical and systemic treatments.

Purpose of the Study:

• To investigate the efficacy of low-frequency ultrasound (20 KHz) in enhancing transdermal transport.
• To compare the transdermal transport enhancement induced by low-frequency ultrasound with that of therapeutic ultrasound.

Main Methods:

• In vitro permeation studies using human cadaver epidermis.
• In vivo permeation experiments utilizing hairless rat skin.
• Assessment of transdermal transport for various permeants including drugs, sugars, and water.

Main Results:

• Low-frequency ultrasound (20 KHz) enhanced transdermal transport of multiple substances across human skin by 3 to 3000-fold.
• A significant enhancement factor of up to 300 was observed for salicylic acid transport across hairless rat skin in vivo.
• No long-term loss of skin barrier properties or damage to living skin was observed with low-frequency ultrasound application.

Conclusions:

• Low-frequency ultrasound is a highly effective method for enhancing transdermal drug transport.
• The observed enhancement is substantially greater than that achieved with conventional therapeutic ultrasound frequencies.
• The mechanism is hypothesized to involve cavitation-induced aqueous channels in the stratum corneum.