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

Most identified drug transporters belong to the ATP-binding Cassette (ABC) and Solute Carrier (SLC) families. Recent research indicates that some of these transporters play an important role in the absorption, distribution and excretion of drugs, and are involved in clinically relevant drug-drug interactions for systemic drugs. However, very little is known about the role of drug transporters in human skin in the disposition of topically applied drugs and their involvement in drug-drug interactions. The aim of this work was to compare the expression in human skin (vs human hepatocytes and kidney) of SLC transporters included in the EMA guidance as the most likely clinical sources of drug interactions. The expression of SLC transporters in human tissues was analyzed by quantitative RT-PCR. Modulation of SLC47A1 and SLC47A2 (MATE1 and MATE2) expression was analyzed after treatment of human skin in organ-culture with rifampicin and UV irradiation. The expression of SLCO2B1 (OATPB), SLCO3A1 (OATPD), SLCO4A1 (OATPE), SLC47A1 and SLC47A2 (MATE1 and MATE2)

IntroductionOnychomycosis is the most common infectious disease involving nails. The aim of this study was to evaluate the antifungal activity of amorolfine 5% nail lacquer and three different acid-based medical devices indicated in the treatment of onychomycosis using an in vitro nail penetration assay.MethodsFour products were tested in vitro: (a) amorolfine 5% nail lacquer; (b) ethyl lactate and acetic acid; (c) citric acid and urea; (d) ethyl lactate, glycerin, lactic acid, and citric acid. Test products were applied to healthy human cadaver nails and allowed to dry. Disks were cut from each piece of nail and placed on seeded agar plates of Trichophyton rubrum. Following incubation at 30 °C, zones of inhibition were measured.ResultsAmorolfine-treated nails exhibited inhibitory activity against T. rubrum with a mean zone of inhibition of 59.2 mm in diameter. In contrast, all three acid-based medical devices and the untreated controls showed no zones of inhibition (mean effective zones of 0 mm).ConclusionIn this in vitro nail penetration model, head-on, comparative study, we showed that amorolfine 5% nail lacquer possesses potent antifungal activity, whereas no antifungal activity was detected for three commercially available acid-based medical devices under identical assay conditions.FundingGalderma.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-016-0093-x) contains supplementary material, which is available to authorized users.

Abrasion with skin preparation pad was shown to be superior to microneedling and iontophoresis for increasing MAL penetration in ex vivo 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.

IntroductionAdapalene 0.1%/benzoyl peroxide 2.5% (0.1% A/BPO) and adapalene 0.3%/BPO 2.5% (0.3% A/BPO) gels are fixed-combination options for the topical treatment of acne. However, the active compounds of these combinations are also available as monads, to be used in association or as monotherapy. These two in vitro studies determined the effect of different treatment regimens on the percutaneous absorption of adapalene (0.1% and 0.3%) gels and BPO 2.5% gel in ex vivo human skin.MethodsIn vitro percutaneous absorption studies were conducted using full-thickness human skin from six donors. Treatment regimens included the application of 0.1% A/BPO, 0.3% A/BPO, or four free-combination regimens of the monads. Skin samples were incubated for 24 h. Concentrations of adapalene and BPO equivalent (BPO-eq) (i.e. benzoic acid after chemical transformation of BPO) were measured using high-performance liquid chromatography. Comparison of regimens was performed using a bioequivalence criterion (estimated ratio bewteen 0.8 and 1.25).ResultsThe fixed combination 0.3% A/BPO regimen demonstrated more than three times higher absorption of adapalene versus the fixed-combination 0.1% A/BPO. Based on the bioequivalence acceptance criterion, all four free-combination regimens were different from 0.1% A/BPO and 0.3% A/BPO, with higher adapalene release delivered by the fixed combinations versus the free combinations. For BPO-eq, the results showed that the free-combination regimens where adapalene 0.1% was applied first were different from 0.1% A/BPO, with lower BPO-eq release delivered by these regimens compared to the fixed combination. The regimen adapalene 0.3% for 10 h followed by BPO 2.5% delivered lower BPO-eq release compared to the fixed combination.ConclusionThe fixed-combination A/BPO gels provide optimal percutaneous absorption of the active compounds compared to free combinations of adapalene 0.1%, adapalene 0.3%, and BPO 2.5%. The higher concentration of adapalene in the 0.3% A/BPO gel and the resulting higher absorption may explain higher clinical efficacy.

In the original publication, in the Methods section, Scholl Fungal Nail Treatment is incorrectly attributed to Bayer Healthcare AG who is neither the manufacturer nor the market authorization holder. This should state Scholl Fungal Nail Treatment, Reckitt Benckiser Healthcare, UK.

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.