Penetration enhancement of two topical 5-aminolaevulinic acid formulations for photodynamic therapy by erbium:YAG laser ablation of the stratum corneum: continuous versus fractional ablation

5-Aminolaevulinic acid (ALA) is used in photodynamic therapy (PDT). Response rates of PDT vary widely, which may be because of the limited uptake of topically applied photosensitisers. We investigated skin penetration and fluorescence induction of protoporphyrin IX (PpIX) after applying either 20% ALA cream or 20% aminolaevulinic acid solution on laser-stripped stratum corneum (SC) in an ex vivo full-thickness porcine skin model. Both formulations are used in clinical practice. To enhance the skin penetration of ALA, we used two different 2940-nm erbium:yttrium-aluminium-garnet (Er:YAG) laser systems to partially ablate the SC: continuous and fractional ablation. Different fluences were applied ranging from 0.5 to 1.5 J/cm2 (continuous ablation) and from 4 to 24 J/cm2 (fractional ablation). Fluorescence microscopy was used for detecting PpIX-induced fluorescence. Compared to skin without laser pretreatment, mean fluorescence intensity (MFI) of PpIX was enhanced 13.8-fold after continuous ablation with 1.0 J/cm2 and 7.3-fold after fractional ablation with 4 J/cm2; each laser procedure was followed by 4-h incubation with lipophilic ALA cream. Optimal parameters for continuous ablation without damage to the epidermis were 1 J/cm2 for both formulations, fractional ablation was best with 4 J/cm2. Histological evaluations of laser-treated skin showed necrosis and apoptosis, depending on light dose. In laser-stripped skin, PpIX fluorescence was detected earlier and reached deeper epidermal layers than in untreated skin. Continuous laser ablation induced higher PpIX fluorescence levels than fractional ablation. This method offers a promising new tool for enhancing ALA penetration in PDT without damaging the underlying tissue.