Permeable Cornified Envelope Layer Regulates the Solute Transport in Human Stratum Corneum

Zakaria, Afshin Zamani; Jepps, Owen G.; Gould, Tim; Anissimov, Yuri German

doi:10.1016/j.xphs.2023.03.002

Cited by 2 publications

(2 citation statements)

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“…In addition to the construction of lipid bilayers, the study of solute diffusion through them holds significance from a pharmacokinetic standpoint, particularly in the context of establishing a macromodel for the entire stratum corneum (SC) layer. 5 The two primary approaches commonly used to investigate the diffusion of substances through the stratum corneum (SC) are experimental methods and molecular dynamics (MD) simulations. Experimental studies have been conducted to determine the diffusion coefficient of solutes in the lateral direction of lipid bilayers.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The CE acts as an almost impermeable barrier to most lipophilic molecules . However, slow diffusion of solutes from the corneocyte envelopes can have a significant impact on the overall solute flux through the stratum corneum . Moreover, the corneocyte cells are surrounded by stacks of lipid bilayers, which serve as the primary pathway for the transport of hydrophobic solutes.…”

Section: Introductionmentioning

confidence: 99%

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Permeability of Dermatological Solutes through the Short Periodicity Phase of Human Stratum Corneum Lipid Bilayers

Zamani Zakaria,

Malde,

Gould

2023

J. Chem. Inf. Model.

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Determining the permeability of drug-like solutes through the densely packed and heterogeneous stratum corneum lipid layer presents a significant challenge. In this study, we employed umbrella sampling with a periodic weighing function applied to the center of mass of the lipid bilayers. Precise umbrella sampling was conducted with an interframe distance of 0.5 Å, spanning from the bilayer center to the water phase, and each frame was simulated for at least 20 ns. Autocorrelation functions, potential of mean force (PMF), and diffusivity profiles were analyzed for six solutes (testosterone, benzene, caffeine, ethanol, mannitol, and histidine). The results revealed that autocorrelations were dependent solely on the medium, whether water or lipid phase. Diffusivity and PMF profiles along the reaction coordinate were influenced by the hydrophilicity of the solute rather than its size. For hydrophobic solutes, the PMF curves exhibited a minimum at the bilayer center, while for hydrophilic solutes, the PMFs peaked at the bilayer center and lipid tails (where the lipid tails are not interacting with the cholesterol). Diffusivity curves were low at the bilayer center and water phase, with peaks observed at the headgroup or the boundary between fatty acid and cholesterol (1 nm from the bilayer center). The quantitative findings presented in this work hold significance for pharmacists and drug designers.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%