Molecular diffusion in the human nail measured by stimulated Raman scattering microscopy

The effective treatment of diseases of the nail remains an important unmet medical need, primarily because of poor drug delivery. To address this challenge, the diffusion, in real time, of topically applied chemicals into the human nail has been visualized and characterized using stimulated Raman scattering (SRS) microscopy. Deuterated water (D ₂O), propylene glycol (PG-d ₈), and dimethyl sulphoxide (DMSO-d ₆) were separately applied to the dorsal surface of human nail samples. SRS microscopy was used to image D ₂O, PG-d ₈/DMSO-d ₆, and the nail through the O-D, -CD ₂, and -CH ₂ bond stretching Raman signals, respectively. Signal intensities obtained were measured as functions of time and of depth into the nail. It was observed that the diffusion of D ₂O was more than an order of magnitude faster than that of PG-d ₈ and DMSO-d ₆. Normalization of the Raman signals, to correct in part for scattering and absorption, permitted semiquantitative analysis of the permeation profiles and strongly suggested that solvent diffusion diverged from classical behavior and that derived diffusivities may be concentration dependent. It appeared that the uptake of solvent progressively undermined the integrity of the nail. This previously unreported application of SRS has permitted, therefore, direct visualization and semiquantitation of solvent penetration into the human nail. The kinetics of uptake of the three chemicals studied demonstrated that each altered its own diffusion in the nail in an apparently concentration-dependent fashion. The scale of the unexpected behavior observed may prove beneficial in the design and optimization of drug formulations to treat recalcitrant nail disease. Significance Diseases of the nail are particularly hard to treat because drug penetration to the target (which lies below the tightly woven keratin network) is extremely limited. To shed greater light on the problem, the diffusion of three pharmaceutically relevant solvents across the human nail has been imaged and characterized by stimulated Raman scattering microscopy. Remarkably, the kinetics of water transport were more than 10-fold faster than those of dimethyl sulphoxide and propylene glycol. Furthermore, the uptake of all three solvents, the diffusion of which appeared to be concentration dependent, progressively undermined the integrity of the nail. These new insights may facilitate the improved formulation of drug products effective in the treatment of dise