Mechanistic Study of Decreased Skin Penetration Using a Combination of Sonophoresis with Sodium Fluorescein-Loaded PEGylated Liposomes with D-Limonene

The study investigated the effect of low frequency sonophoresis (SN) on the skin transport of sodium fluorescein (NaFI)-loaded liposomes. It was found that SN significantly increased the flux of NaFI solution but decreased the flux of NaFI-loaded PEGylated liposomes with D-limonene (PL-LI). SN did not significantly affect the flux of NaFI-loaded conventional and PEGylated liposomes. In blocked hair follicles, the flux of NaFI-loaded PL-LI decreased with and without SN, suggesting penetration via the transfollicular pathway. Confocal laser scanning microscopy showed that without SN, NaFI-loaded PL-LI was present in the skin and along hair lengths, while with SN, it was only on the hair surface. Scanning electron microscopy indicated that SN dislocated corneocytes and reduced PL-LI deposition around follicles, suggesting SN may partially block follicle orifices and reduce absorption through the follicular pathway.