title: A HCl/alcohol formulation increased 5-aminolevulinic acid skin distribution using an ex vivo full thickness porcine skin model.
abstract: 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.
authors.affiliation: Department of Dermatology, University of Regensburg, Regensburg, Germany. tim.maisch@klinik.uni-regensburg.de
authors.forename: Tim
authors.initials: T
authors.lastname: Maisch
authors.forename: Christine
authors.initials: C
authors.lastname: Worlicek
authors.forename: Philipp
authors.initials: P
authors.lastname: Babilas
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.forename: Rolf-Markus
authors.initials: RM
authors.lastname: Szeimies
mesh_terms: D000438:Alcohols / Q000493:pharmacokinetics* / Q000633:toxicity; D000622:Aminolevulinic Acid / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D005260:Female; D006851:Hydrochloric Acid / Q000493:pharmacokinetics* / Q000633:toxicity; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000633:toxicity; D011524:Protoporphyrins / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D053832:Surgical Tape; D034421:Sus scrofa
chemical_list: D000438:Alcohols; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D006851:Hydrochloric Acid