Sonophoresis enhances the skin penetration of 5‐aminolevulinic acid: A promising pretreatment for photodynamic therapy

5-aminolevulinic acid (5-ALA) has a poor penetrance of the skin with topical application, which reduces the efficacy of photodynamic therapy (PDT). Sonophoresis involves the use of sound waves or ultrasonic energy to enhance the topical or transdermal delivery of drugs. The purpose of this study was to investigate the effects of sonophoresis on the penetration of 5-ALA into the skin. We calculated in vitro transdermal accumulation of ALA, and the fluorescence images were collected for analysis. The cumulative amount of 5-ALA that penetrated the skin with sonophoresis increased over time and was significantly larger than that without sonophoresis (p < 0.01). With 5% 5-ALA and sonophoresis, the distinct localization of 5-ALA-PpIX in sebaceous glands started to appear 30 min after 5-ALA application, which is much earlier than with 5% 5-ALA only. For all incubation times, fluorescence intensities distributing in sebaceous glands were significantly higher in sonophoresis treated than non-sonophoresis treated skin (p < 0.05). Sonophoresis could be a technique of choice for enhancing the production of 5-ALA-induced PpIX and improving the efficacy of 5-ALA-based PDT, which may decrease the treatment time, lower the cost of therapy and enhance the clinical improvement, allowing many more patients to be treated.