Xenon as a transdermal enhancer for niacinamide in Strat-M™ membranes

Abstract

Xenon is confirmed to diffuse readily through membranes and has properties of transdermal enhancer. In this study, the ability of xenon to regulate the transdermal diffusion of niacinamide was investigated using a model of an artificial skin analogue of Strat-M™ membranes in Franz cells. Based on the data obtained, we found that in the simplified biophysical model of Strat-M™ membranes xenon exerts its enhancer effect based on the heterogeneous nucleation of xenon at the interfaces in the microporous structures of Strat-M™ membranes.

Keywords: Franz cell; Strat-M; enhancer; gas nucleation; niacinamide; permeation; skin; transdermal drug delivery system; xenon.

Figure 1

Cumulative xenon flux in the absence of a barrier and through Strat-M™ membranes. Note: Data are presented as mean ± SD. The experiments were repeated five times. *P < 0.05, no barrier group (n = 5) vs. Strat-M™ membranes group (n = 4) (one-way analysis of variance followed by Scheffe post hoc test).

Figure 2

Dose-dependent effect of xenon on transdermal diffusion of niacinamide across Strat-M™ membranes. Note: (A) Enhancing effect of 0.5× xenon concentration (n = 12) on niacinamide transmembrane flux compared to nicainamide flux without xenon (n = 9). (B) Same as in A, but 1× xenon concentration was used (n = 9). (C) A lower (0.5×) xenon concentration results in a partial increase of xenon properties as an enhancer compared to the maximum 1× xenon concentration. Comparison of the niacinamide accumulation curves for the 1× and 0.5× cases shows that the diffusion of niacinamide for the 0.5× case is enhanced during the first 4 hours. Data are presented as mean ± SD. *P < 0.05 (one-way analysis of variance followed by Scheffe post hoc test).

Figure 3

Nucleation of xenon on Strat-M™ membranes. Note: (A) View from the cut side of the membrane 5 minutes after immersion in phosphate-buffered saline maximally saturated with xenon (1×). (B) View from the dermal side of the membrane 35 minutes after immersion. Arrows indicate forming xenon bubbles. Scale bars: 0.3 mm.

Figure 4

The proposed mechanism of xenon as an enhancer in Strat-M™ membranes. Note: (A) Niacinamide diffuses freely through the membrane (no xenon). (B) Maximum saturation (1×) xenon nucleation at the internal interfaces accompanied by partial overlapping of niacinamide diffusion pores due to the formation of massive bubbles (the enhancer effect of xenon is weakened). (C) Half saturation (0.5×) xenon nucleation on the hydrophobic parts of the membrane facilitates niacinamide diffusion (xenon is acting as an enhancer).