A quantitative radioluminographic imaging method for evaluating lateral diffusion rates in skin

Rush, Allison K; Miller, Matthew A.; Smith, Edward D.; Kasting, Gerald B.

doi:10.1016/j.jconrel.2015.07.032

Cited by 14 publications

(9 citation statements)

References 36 publications

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“…b) . This rigid arrangement results in a sparse water solubility of 10–20 ppm , and therefore in commercial products, Zn(PT) 2 exists as particles dispersed in chemically intricate formulations . One of the major applications is in antidandruff shampoos, and it is this incorporation of the zinc complex into cleansers that has prompted manufacturers to optimize the size and shape of Zn(PT) 2 particles.…”

Section: Introductionmentioning

confidence: 99%

Optical Characterization of Zinc Pyrithione

Sandiford

Holmes

Mangion

et al. 2019

Photochem & Photobiology

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Zinc pyrithione is ubiquitous in commercial products particularly antidandruff shampoos. For the efficacy of zinc pyrithione therapeutic cleansers to be assessed accurately, the distribution of particles on the scalp needs to be visualized. Currently, no technique is available which provides the chemical specificity and sensitivity required. Here, we report application of fluorescence‐lifetime imaging microscopy (FLIM) for high‐contrast mapping of zinc pyrithione distribution on the scalp. Characterization of the zinc pyrithione emission by using both one‐photon excitation at five specific wavelengths and two‐photon excitation in the range of 740–820 nm revealed its FLIM fingerprint—a characteristic short average time‐weighted emission lifetime of ΤZnPT = 250 ps. Bandpass‐filtering FLIM signals at ΤZnPT enabled an efficient discrimination between the zinc pyrithione and major endogenous skin species in comparison with that of the conventional reflectance confocal microscopy. Our findings provide means for in vivo high‐sensitivity assaying and high‐contrast imaging of zinc pyrithione in biological systems.

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Section: Introductionmentioning

confidence: 99%

Optical Characterization of Zinc Pyrithione

Sandiford

Holmes

Mangion

et al. 2019

Photochem & Photobiology

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“…xx have been recently reported. [40][41][42] More recently, Yu and Kasting 43 have used a diffusion model based on hexagonally distributed shunts to obtain best-fit values of the lateral to transdermal effective diffusivity ratio from desorption data for hydrophilic solutes, with an emphasis on characterizing polar pathways. Aside from numerical results implicit in homogenization calculations of the full tensorial effective diffusivity, 6,24 diffusion in the plane of the skin seems to have been modeled only at the macroscopic scale to date [see Naegel et al 6 (text on p. 198 and Fig.…”

Section: Scmentioning

confidence: 99%

“…Effective Lateral Diffusivity Quantifying Solute Spreading in the Plane of the SC Rush et al 40 report lateral diffusion coefficients for four solutes, including testosterone and caffeine, determined by radioluminographic imaging of radial spreading over time of a 2 mL Table 7 Approximate Components of the Dimensionless Effective Diffusivity Tensor for the Microstructures Shown in Figure 1, Based on Equations 21-24, for Comparison With Table 6 Line Entries in this table are obtained by using Equations 21-24 in place of numerically calculated average solute fluxes jb pj À1 b p$j v and jb qj À1 b q$j v through the burgundy and dark blue contours marked in Figure 7, respectively. The approximate results are substituted into the equations given in Table 3, sections c and d. The first two lines are identical because the approximate theory applies to vanishingly small lacunae and does not distinguish between different values of r lip .…”

Section: Analytical Formulasmentioning

confidence: 99%

“…Equations 21-24 (together with the formulas in Table 3, sections c and d) could be used with reasonable accuracy for D lip ⊥ =D lip k > 10 À4 . Further work should be directed toward a comprehensive tabulation of the universal dimensionless coefficients d xx , more comprehensive comparisons with the growing body of experimental data on lateral diffusion in the plane of the SC [40][41][42][43] would be worthwhile.…”

Section: Recommendations For Real Scmentioning

confidence: 99%

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Microscopic Models of Drug/Chemical Diffusion Through the Skin Barrier: Effects of Diffusional Anisotropy of the Intercellular Lipid

Nitsche

Kasting

Nitsche

2019

Journal of Pharmaceutical Sciences

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Owing to the systematic alignment and ordering of fatty acid and ceramide chains, lipid layers in biological membranes have strongly anisotropic diffusion properties. The diffusivity D lip k for solute transport in the direction parallel to the lipid layer is typically 10 3-10 5 times the diffusivity D lip ⊥ for the perpendicular direction. This article explores the consequences of this strong degree of anisotropy on solute diffusion through the stratum corneum (barrier) layer of the skin based on a realistic representation of a unit cell of the microstructure. Complementary numerical methods (smoothed particle hydrodynamics, finite differences) are used to solve the steady-state unit-cell diffusion problem leading to the average (homogenized, coarse-grained) diffusion tensor characterizing the tissue as an effective continuum. A parametric study is presented characterizing solute concentration profiles in detail for testosterone-and caffeine-like permeants, and it is shown that the results cannot be mimicked by calculations based on an isotropic lipid-phase diffusivity. The ratio of lateral to transdermal effective diffusivities calculated by the present model is of the order of 40 and 300 for fully hydrated (in vitro) and partially hydrated (in vivo) states, respectively. These values compare favorably with the results of recent experiments.

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“…Due to its effective barrier properties, skin is of significant interest to controlled release of pharmaceutical and other products (1,2). In the past, research in this field largely relied on in vivo, ex vivo and in vitro tests (especially in early phase development), and clinical studies with human volunteers (typically in late phase trials).…”

Section: Introductionmentioning

confidence: 99%

In Silico Modelling of Transdermal and Systemic Kinetics of Topically Applied Solutes: Model Development and Initial Validation for Transdermal Nicotine

2016

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PurposeThe purpose was to develop a mechanistic mathematical model for predicting the pharmacokinetics of topically applied solutes penetrating through the skin and into the blood circulation.The model could be used to support the design of transdermal drug delivery systems and skin care products, and risk assessment of occupational or consumer exposure.Methods A recently reported skin penetration model [Pharm Res 32 (2015) 1779] was integrated with the kinetic equations for dermis-to-capillary transport and systemic circulation. All model parameters were determined separately from the molecular, microscopic and physiological bases, without fitting to the in vivo data to be predicted. Published clinical studies of nicotine were used for model demonstration. ResultsThe predicted plasma kinetics is in good agreement with observed clinical data. The simulated two-dimensional concentration profile in the stratum corneum vividly illustrates the local sub-cellular disposition kinetics, including tortuous lipid pathway for diffusion and the "reservoir" effect of the corneocytes. Conclusions

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A quantitative radioluminographic imaging method for evaluating lateral diffusion rates in skin

Cited by 14 publications

References 36 publications

Optical Characterization of Zinc Pyrithione

Optical Characterization of Zinc Pyrithione

Microscopic Models of Drug/Chemical Diffusion Through the Skin Barrier: Effects of Diffusional Anisotropy of the Intercellular Lipid

In Silico Modelling of Transdermal and Systemic Kinetics of Topically Applied Solutes: Model Development and Initial Validation for Transdermal Nicotine

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