A HCl/alcohol formulation increased 5-aminolevulinic acid skin distribution using an ex vivo full thickness porcine skin model

Topical photodynamic therapy with 5-aminolevulinic acid (5-ALA) is a newly established treatment modality for epithelial skin cancer. Skin distribution of different 20% 5-ALA formulations was investigated by detection of protoporphyrin IX (PpIX) using an ex vivo porcine skin model. Fluorescence of PpIX was first detectable at 2 h after application of a 5-ALA/HCl-alcohol solution, followed by a 5-ALA gel +/- 40% DMSO > 5-ALA lipophilic ointment > 5-ALA hydrophilic ointment at 4 h after application. Intensity of PpIX was 10-fold higher after 5-ALA/HCl-alcohol application in contrast to 5-ALA hydrophilic ointment. Maxima of PpIX fluorescence were measured between 18 and 24 h after application. PpIX accumulation induced by 5-ALA within the lower parts of the epidermis was increased in order of 5-ALA hydrophilic ointment < 5-ALA lipophilic ointment < 5-ALA gel w/o DMSO < 5-ALA gel with DMSO < 5-ALA/HCl-alcohol. Illumination of skin incubated with different 5-ALA formulations led to a marked increase of apoptotic cells in the epidermis depending on the penetration depth of the 5-ALA formulations. A formulation containing short chain alcohols have been observed to increase the permeation and distribution of 5-ALA. PpIX fluorescence was detected earlier yielding to photodynamic effective amounts of PpIX in the epidermis as compared with all other 5-ALA formulations used. These data emphasizes the potential of investigating properties of new formulations using such a full thickness porcine skin model.