Unraveling the Molecular Mechanisms of Alcohol-Mediated Skin Permeation Enhancement: Insights from Molecular Dynamics Simulations.
Level 5 - mechanism / opinion, no new human data
In silico molecular dynamics simulation (mechanism-based reasoning)
PubMed 38115608 · doi:10.1021/acs.langmuir.3c02809
What was done
Molecular dynamics (MD) simulations were used to examine the effects of three alcohols—1,2-propanediol (1,2-PDO), 1,2-butanediol (1,2-BDO), and ethanol (EtOH)—on a stratum corneum (SC) model lipid membrane. Constrained simulations were subsequently performed to determine the free energy barriers to the permeation of a hydrophilic model molecule across the membrane.
What was found
The abstract reports no numerical values or statistical metrics. Qualitatively, the alcohols exerted concentration-dependent effects by interacting with SC lipids and selectively extracting free fatty acid (FFA) molecules, which loosened the SC structure. At higher concentrations, 1,2-BDO and EtOH penetrated the lipid bilayers, creating continuous hydrophilic defects, increasing ceramide tail chain disorder and fluidity, and weakening lipid hydrogen bonding. These structural changes reduced the free energy barrier for hydrophilic model molecule permeation, particularly for 1,2-BDO and EtOH.
Why it matters
Elucidates the atomic-level mechanisms by which common alcohol permeation enhancers disrupt the stratum corneum barrier, offering structural insights for optimizing transdermal drug delivery systems.
Limits
Findings rely entirely on simplified in silico model membranes rather than intact human or animal skin. No physical in vitro or in vivo permeation experiments were conducted to validate the computational predictions, and the abstract provides no specific quantitative concentrations, energetic values, or statistical measures.
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