The present findings are the first to demonstrate the involvement of MRP1 in drug uptake in human skin.

The present study investigated the effects of microneedle roller device on dermal delivery of Rhodamine 123 on ex vivo human skin. The effect of microneedle treatment on transepidermal water loss (TEWL) was also evaluated. Permeation studies of Rhodamine 123 through full-thickness human skin were conducted using modified Franz diffusion cells. The results showed that TEWL increased with the number of passes of the roller device. In addition, results of the in vitro permeation studies revealed marked increase of the absorption and the distribution of Rhodamine 123 through microneedle-treated skin. The increase of skin absorption was dependent on needle length. Thus, microneedle roller device markedly increased the absorption and distribution of Rhodamine 123 in ex vivo human skin and could be suitable for clinical and preclinical use in order to enhance dermal delivery of test molecules.

IntroductionPre-treatment of the skin to remove scales and crusts prior to photodynamic therapy (PDT) is essential to enhance the uptake of topically applied methyl aminolevulinate (MAL) and to improve treatment efficacy. This study compared the effect of two different skin preparation pads on skin integrity in ex vivo human skin.MethodsEx vivo human skin samples from three donors were pre-treated in triplicates with PREPSTER™ (PR) skin preparation pad (6, 8, and 10 passages) or Ambu Unilect™ (A-UN) skin preparation pad (6, 8, and 10 passages). In addition, skin samples were pre-treated with tape strippings (10 adhesive tape strips) as a reference method for comparison. Transepidermal water loss (TEWL) was measured on intact skin and following skin barrier impairment using skin preparation pads and tape stripping. Histological analysis was performed to verify the impairment of the stratum corneum (SC) barrier function in samples from intact skin (control), 10 tape strippings (reference method), 10 passages of PR, and 10 passages of A-UN.ResultsTEWL increased with the increasing number of passages of skin preparation pads, with 2.4- and 3.3-fold increases following 10 passages of A-UN and PR, respectively, versus a 2.2-fold increase with 10 tape strippings (reference). Histological analysis showed only partial removal of the SC, with no damage observed on the epidermis, regardless of the procedure used.ConclusionPre-treatment of skin using PR and A-UN skin preparation pads markedly increases TEWL, indicating slight impairment of the SC barrier function. Comparison of both skin preparation pads showed that PR pad consistently induced significantly higher TEWL than A-UN pad (p < 0.05), regardless of the number of passages. Both skin preparation pads are thought to increase the uptake of MAL and can therefore be used for the preparation of skin prior to PDT.FundingNestlé Skin Health – Galderma R&D.

The results showed that the in vitro skin penetration of MAL and the PpIX photoactivation on ex vivo human skin samples are not modified by pretreatments of ex vivo human skin with sunscreens. This study demonstrates that neither in vitro skin penetration of MAL nor PpIX photoactivation were modified by pretreatments with Cetaphil SPF 30 Dermacontrol and Actinica Lotion SPF 50+. This supports the efficacy and safety of MAL DL-PDT in the clinical situation.