Photosensitizing\nProperties of the Topical Retinoid\nDrug Adapalene

Photoreactivity is an important issue\nfor topical drugs especially\nwhen these are applied on the sun-exposed skin area. In this context,\nthird-generation retinoids are of special interest due to their conjugated\nchemical structure and their use in the treatment of acne. Herein,\nthe phototoxic potential of one of these drugs, adapalene, is established\nusing an in vitro 3T3 Neutral Red Uptake (NRU) test. Photophysical\nstudies demonstrate the involvement of a Type II process with an efficient\nformation of singlet oxygen. Interestingly, quenching of the adapalene\nsinglet manifold by oxygen leads to an increased production of this\nreactive oxygen species through the tagged O<sub>2</sub>-enhanced\nintersystem crossing process. Taken together, these results are relevant\nfrom a toxicological point of view as adapalene could be considered\nas a double-edged sword: it can be at the origin of undesired skin\nphotosensitivity reactions or be considered as a candidate for topical\nphotodynamic therapy.