Percutaneous absorption of three psoralens commonly used in therapy: Effect of skin occlusion (in vitro study)

Abstract

Occlusion is recognised as an enhancer of percutaneous absorption. Some authors suggested that this effect is related to the molecular polarities of applied drugs. To verify this hypothesis, an in vitro study was performed to assess a topical absorption, under occlusion, in relation to the molecular polarity of three furanocoumarins: 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP) and trimethylpsoralen (TMP). These compounds present the same basic chemical structure but have different degrees of lipophilicity. They are commonly used, orally or topically, in conjunction with UVA irradiations to treat skin diseases such as psoriasis and vitiligo. Ethanolic solutions of the psoralens were deposited onto human abdominal skin fragments (6.3 μg/cm 2), mounted on Franz® diffusion cells ( n = 12), which were maintained at 37°C. Occlusion was retained by placing rubber corks on the top of Franz® cells ( n = 6). The receptor fluid was constituted with 1.4% of human serum albumin solution. At each sample point (2, 4, 6, 8, 12 and 24 h), the entire content of the receptor chamber was removed and replaced by fresh albumin solution. Psoralens quantities in the removed solutions were determined by HPLC. The lipophilicity of the psoralens was established via the partition coefficient in an octanol/water system: TMP > 5-MOP > 8-MOP. The outcome of the results illustrates that occlusion does not always have an enhancing effect in percutaneous absorption. Occlusion impact is influenced by the polarity of the drug. It increases the absorption of moderately lipophilic molecules (i.e. 8-MOP, 5-MOP) but is almost ineffective on the absorption rate of molecules highly lipophilic (i.e. TMP).