Visualizing dermal permeation of sodium channel modulators by mass spectrometric imaging

Abstract

Determining permeability of a given compound through human skin is a principal challenge owing to the highly complex nature of dermal tissue. We describe the application of an ambient mass spectrometry imaging method for visualizing skin penetration of sodium channel modulators, including novel synthetic analogs of natural neurotoxic alkaloids, topically applied ex vivo to human skin. Our simple and label-free approach enables successful mapping of the transverse and lateral diffusion of small molecules having different physicochemical properties without the need for extensive sample preparation.

Figure 1

Penetration of the sodium channel blocker compounds tested in human skin of the same donor using ethanol as the vehicle. Chemical structures are shown for (a) saxitoxin, (d) lidocaine, (g) aconitine, and (j) BTX-A. Positive ion mode DESI-MS ion images of the compounds are shown for human skin in which (b) saxitoxin, (e) lidocaine, (h) aconitine, and (k) BTX-A were topically applied. Optical images of cross sections of the same tissue sections imaged by DESI after H&E stain are shown in (c) for saxitoxin, (f) for lidocaine, (i) for aconitine, and (l) for BTX-A.

Figure 2

Penetration of novel synthetic analogue tested in human skin of the same donor. The chemical structure of STX-ge is shown in (a). Positive ion mode DESI-MS ion images of the compound are shown for human skin in which STX-ge was topically applied using (b) ethanol and (d) DMSO as vehicles. Optical images of the same tissue sections imaged by DESI after H&E stain are shown in (c) and (f), respectively. DESI mass spectra of selected skin regions outlined with a small black box in the optical images in (c) and (f) are shown for STX-ge (d) in ethanol and (g) in DMSO.

Figure 3

DESI-MS ion images showing the penetration of (a) aconitine, (b) BTX-A and (c) STX-ge tested in human skin of the same donor using EMLA cream. Ion images showing the penetration of lidocaine and prilocaine, compounds with are both present in the EMLA cream formulation, are also presented for the three sections analyzed.

Figure 4

DESI-MS ion images showing the penetration of aconitine tested in in vivo rat skin using (a) ethanol and (b) DMSO as vehicles. Optical images of the same tissue sections imaged by DESI after H&E stain are also shown.