Abstract

Low frequency ultrasound (LFU) enhances skin permeability via the formation of heterogeneous localized transport regions (LTRs). In this work, hydrogels with different zeta potentials were used as the coupling medium for LFU to investigate their contribution to LTR patterns and to the skin penetration of two model drugs, calcein and doxorubicin (DOX). When hydrogels were used, LTRs covering at least a 3-fold greater skin area were observed compared to those resulting from traditional LFU treatment and sodium lauryl sulfate. More LTRs resulted in an enhancement of calcein skin permeation. The zeta potential of the hydrogels affected the skin penetration of the positively charged DOX; the cationic coupling medium decreased the DOX recovered from the viable epidermis by 2.8-fold, whereas the anionic coupling medium increased the DOX accumulation in the stratum corneum by 4.4-fold. Therefore, LFU/hydrogel treatment increases LTRs areas and can target ionized drugs to specific skin layers depending on the zeta potential of the coupling medium.

Highlights

  • Low frequency ultrasound (LFU) enhances skin permeability via the formation of heterogeneous localized transport regions (LTRs)

  • Several studies have conclusively shown that low frequency ultrasound (LFU) skin permeabilization is mediated by transient cavitation, which creates LTRs in the skin surface when skin is pre-treated using 1% sodium lauryl sulfate (SLS) as coupling medium (LFU/SLS)[2,6,7,8]

  • The formation of LTRs in the skin surface occurs heterogeneously, covering only approximately 5–10% of the total area of the skin exposed to LFU/SLS12,13,15,31

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Summary

Introduction

Low frequency ultrasound (LFU) enhances skin permeability via the formation of heterogeneous localized transport regions (LTRs). LFU/hydrogel treatment increases LTRs areas and can target ionized drugs to specific skin layers depending on the zeta potential of the coupling medium. At 20 kHz, the most studied frequency in LFU transdermal drug delivery, only 5–10% of the treated skin surface area results in LTR formation, even when long treatment times are used[6,12,14,18]. Modifications in the coupling medium to change bubble nucleation has been attempted to increase LTR formation and skin permeability[7,13,19,20,21,22]. Hydrogels are often used in HFU as a coupling medium[24,25], there are no reports in the literature of their use in LFU

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