Elucidation of the transport pathway in hairless rat skin enhanced by low-frequency sonophoresis based on the solute–water transport relationship and confocal microscopy

Potential and problems in ultrasound-responsive drug delivery systems

“…62,63 The horn-to-skin distances used range from the ultrasound horn being in direct contact with the skin (zero distance) to 4.0 cm. 62 The most common distance with low-frequency sonophoresis ranges from 0.3 cm to 1.0 cm, [63][64][65] and is much smaller than for high-frequency sonophoresis. Treatment times can vary from a few seconds 66,67 to a few minutes, 36,60 to hours to days.…”

Mechanistic study of decreased skin penetration using a combination of sonophoresis with sodium fluorescein-loaded PEGylated liposomes with D-limonene

“…The transdermal delivery of hydrophilic solutes with low-frequency ultrasound is likely to occur as non-specific transport across the stratum corneum (ie, both the intracellular lipid regions and the corneocytes). 4 Several possible mechanisms for SN as a transport pathway have been suggested, such as thermal effects by absorption of ultrasound energy and cavitation effects caused by collapse and oscillation of cavitation bubbles in the ultrasound field. 5,6 Cavitation has been found to be the main factor in creating aqueous pathways across the stratum corneum by distorting the lipid bilayer, which can lead to enhancing the transport of hydrophilic drugs across the skin.…”

“…The mechanism of SN is acoustically induced cavitation to create intercellular lipid channels and defects in the stratum corneum both in the lipid bilayer and in the corneocyte, which induces aqueous permeation pathways at discrete sites. 4,9,25 In SN, both cavitation and temperature affect the solute diffusivity. Thermal energy provides a doubling of permeability for every 10°C of increase in temperature.…”

“…Morimoto et al reported that the differences in the physicochemical properties of the solutes, such as lipophilicity or hydrophilicity, may be affected when using low frequency ultrasound, as the ultrasound increases water transport across the skin. Thus, the distribution of more lipophilic compounds may not be influenced, 4 indicating that PL-LI as a lipid vesicle carrier might not penetrate through hydrophilic transport routes in the intercellular space of the stratum corneum. In addition, liposomes adsorbed onto the skin damage caused by sonication might cause the high fluorescence intensity of both NaFI and Rh-PE-labeled CL and PL at the top of the skin layer.…”

“…The lowfrequency SN induces disruption of the structure of stratum corneum lipid bilayers and enhances skin permeability for hydrophilic molecules in solution into the viable epidermis through an intracellular pathway. 4,8 However, the combination of CL or PL with SN for treated skin showed small corneocytes lifting, indicating that the lipid membrane of liposomes could fill and cover the skin damage. Although liposomes can repair the skin damage, the combination of using a chemical penetration enhancer (d-limonene) in a liposomal formulation (PL-LI) and SN resulted in greater disruption of the skin stratum corneum so the skin damage could not be repaired by liposomes.…”