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Purpose: The purpose of the study was to sort skin penetration of anions with respect to their properties and to assess their mechanisms of penetration., Methods: Aqueous solutions of halides at two concentrations were prepared and quantitative penetration studies were carried out for 24 h using Franz diffusion cells. The iodide permeation was also measured after blocking of anion channels and transporters to investigate the role of this specific transport., Results: Absorption of halide ions into skin revealed large differences of transport between these anions according to the Hofmeister series. Increasing steady-state fluxes and lag times in the order F(-) < Cl(-) < Br(-) < I(-) were observed in permeation experiments. The steady-state fluxes were proportional to the concentration for each halide ion. Longer lag times for iodide or bromide ions were explained by the ability of such sticky chaotropic anions to interact with apolar lipids especially in the stratum corneum. Inhibiting ion exchangers and channels decreased the flux of iodide ions by 75%, showing the high contribution of the facilitated transport over the passive pathway., Conclusion: Ions transport had contributions coming from passive diffusion through the skin layers and transport mediated by ion channels and binding to ion transporters.

Purpose: Measurement of skin absorption of ions requires specific experimental protocols regarding the use of pig skin as a model, the viability of excised skin in water medium over 24 h, the presence of endogenous ions, and evaluation of the contributions of facilitated transport through ion channels and ion transporters., Method: Absorption experiments of halide anions F(-), Cl(-), Br(-) and I(-) in excised skin were performed in Franz diffusion cells. Experiments were performed on human and porcine skin under various conditions so as to define and validate experimental protocols., Results: The distributions of endogenous ions and the absorption kinetics of halide ions were similar in both porcine and human skin models. Fresh skin kept its viability over 24 h in salt-free water, allowing experiments following OECD guidelines. Permeation increased in the order F(-) < Cl(-) < Br(-) < I(-) for all receptor media and skin samples. Absorption was larger in fresh skin due to the transport through chloride channels or exchangers., Conclusion: Skin absorption experiments of ions in Franz cells rely on working with fresh excised skin (human or porcine) and pure water as receptor fluid. Experiments with chloride blockers or frozen/thawed skin allow discriminating passive diffusion and facilitated transport.

Purpose: We aimed to investigate the influence of microemulsion nanoscale organization as either oil-in-water droplets, water-in-oil droplets, or bicontinuous structures on skin delivery of drugs assisted by microemulsions., Methods: Three microemulsions of different microstructure, o/w, w/o, and bicontinuous at the skin temperature (32°C), having the same oil and water contents and containing the same ingredients were selected using the Kahlweit fish phase diagrams method. The microemulsions are quaternary mixtures of the Polysorbate 21 (Tween®21) and Sorbitan monolaurate (Span®20) surfactants, isononyl isononanoate oil and water. The microemulsion nanostructure was characterized by electrical conductivity, Pulsed Field Gradient Spin-Echo NMR and Small-Angle Neutron Scattering measurements. The Franz cell method was used to monitor skin absorption of caffeine loaded in microemulsions over 24 h exposure to excised pig skin., Results: Three microemulsions with the three structures were selected, keeping the same composition but the Tween®21/Span®20 ratio. The transdermal flux of caffeine was in the order aqueous solution ≈ w/o < bicontinuous < o/w microemulsion. The o/w microemulsion allows the permeation of 50% of the applied dose within 24 h., Conclusions: The structure of microemulsions is of relevance for skin absorption. The water-continuous structures allow faster transport of hydrophilic drugs.

Purpose: Confocal Raman microspectroscopy (CRM) was used to follow the absorption of retinol into the skin and to track the absorption of ingredients in topically applied formulations., Method: Three surfactants, PEG20C12, PEG20C18:1 (hydrophilic) and PEG6C18:1 (lipophilic), were used in preparing three o/w emulsions and three surfactant solutions all containing retinol. Quantitative retinol penetration studies for 24 h were carried out using Franz diffusion cells. CRM was used to follow the skin penetration of retinol, oil and water and also to study a possible modification of the lipid skin barrier in the stratum corneum (SC) using the ratio of I(2880)/I(2850)., Results: The oily surfactant solution containing PEG6C18:1 and dodecane showed the highest retinol penetration rate. This appears to be related both to the short polar head group of the surfactant and to the effect of dodecane on skin lipids. All the surfactant solutions showed a higher penetration rate compared with the corresponding emulsions. CRM measurements showed that the ratios of I(2880)/I(2850) were significantly modified using surfactant solutions., Conclusions: Penetration behavior appeared to be dependent on the surfactant used in the formulation. CRM associated to the Franz cell method gives new insights on permeation of drug related to vehicle or ingredients.