Diffusion of uncharged solutes through human nail plate

Abstract

Passive diffusion data for uncharged solutes in hydrated human nail plate are collected and compared to the predictions of two theories for diffusion of uncharged solutes in dense keratin matrices. Quantitative agreement between the experimental data and the theories examined is poor. Concerns with both the experiments and the theories are identified and discussed. It is evident from the analysis that magnitude of the experimental nail permeability data may be questioned, as may the extrapolation procedures used to estimate the properties of dense fiber arrays from more dilute systems. Despite these caveats, it can be inferred that the microstructure of the nail plate is more complex than that assumed in the described models. The influence of residual lipids is implicated. More rigorous experiments and theoretical analysis of mass transport in the nail plate system are warranted. Successful completion of these tasks could lead not only to better predictions of transungual drug delivery, but also to better models of skin permeability, if hydrated nail plate can indeed serve as a model for the corneocyte phase of (partially hydrated) stratum corneum.

Size and Charge Dependence of Ion Transport in Human Nail Plate

“…Nevertheless, we show in Fig. 3 that the present estimates of the ratio D 0 nail / D 0 soln are comparable to a similar ratio calculated for uncharged solutes in nail by Baswan et al 27 The conductivity data are more precise than the passive diffusion data and allow a better estimate of the size dependence of diffusion for solutes in the 1–5 Å range. A modest extrapolation of the regressions given in Eq.…”

“…4b. For the nail, we considered also the fiber matrix models for uncharged solutes described in Baswan et al 27 (see Supplemental Material). As in that report, neither of the models considered accurately described the results.…”

“…3, combined with appropriate electrostatic coupling, 52 can be anticipated to yield plausible diffusion constants in human nail plate for therapeutic antifungal drugs having radii of 5–7 Å. 27 …”

“…Sulfate ion (open diamond) was excluded from the regression analysis. The red crosses represent passive diffusion data for uncharged solutes in nail assembled by Baswan et al 27 …”

“…Results are compared to similar information obtained recently for charged solutes in human stratum corneum 25 as amended 26 and to passive diffusion data for uncharged solutes in human nail plate. 27 A procedure for using the conductivity results to predict transungual iontophoretic drug delivery is proposed.…”