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• W2013688458 endingPage "1254" @default.
• W2013688458 startingPage "1242" @default.
• W2013688458 abstract "The permeability of compromised skin barrier was investigated in vitro using acetone-disrupted hairless mouse skin as a model membrane. The effect of compound lipophilicity was studied using sucrose, caffeine, hydrocortisone, estradiol, and progesterone as model compounds. The results demonstrated that permeability barrier disruption by acetone treatment significantly enhanced the permeability of the skin to both hydrophilic and amphipathic compounds, including sucrose, caffeine and hydrocortisone. This effect was more prominent with caffeine and hydrocortisone at different transepidermal water loss (TEWL) levels. Acetone treatment, however, didn't appear to alter the percutaneous penetration of highly lipophilic compounds, such as estradiol and progesterone. The characteristics of skin permeability were described by parabolic relationships between log P(WS) (permeability coefficient of whole skin) and log K(O/W) (octanol/water partition coefficient) at different degrees of permeability barrier disruption. The optimal log K(O/W) of compounds for skin penetration appeared to decrease with an increase in TEWL levels. The maximal permeability achieved was similar through skin displaying different TEWL levels. In an attempt to explore the underlying mechanisms for the changes in skin permeability, the stratum corneum/normal saline partition coefficients of water, caffeine, and hydrocortisone either decreased or remained unaffected with an increase in TEWL. Electron microscopic examinations have revealed reductions in stratum corneum lipid content and alterations in intercellular membrane structures as a result of acetone treatment, whereas negligible changes in the number of horny layers were observed by safranin staining of the stratum corneum. We have concluded that the enhancement in skin permeability to both hydrophilic and amphipathic compounds by acetone treatment arose mainly because of the increase in stratum corneum diffusivity at higher TEWL levels. The results imply the possibility of using both TEWL and drug lipophilicity to predict alterations in skin permeability and hence the dose adjustment of topically applied medication for patients with impaired skin barrier function." @default.
• W2013688458 created "2016-06-24" @default.
• W2013688458 creator A5012870190 @default.
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• W2013688458 date "2001-09-01" @default.
• W2013688458 modified "2023-10-16" @default.
• W2013688458 title "Effect of barrier disruption by acetone treatment on the permeability of compounds with various lipophilicities: Implications for the permeability of compromised skin" @default.
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• W2013688458 doi "https://doi.org/10.1002/jps.1077" @default.
• W2013688458 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11745777" @default.
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