Molecular weight dependence of polyethylene glycol penetration across acetone-disrupted permeability barrier |
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Authors: | Tsai J C Hung P L Sheu H M |
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Institution: | (1) Institute of Clinical Pharmacy, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, Taiwan 70101 e-mail: jctsai@mail.ncku.edu.tw, Tel.: +886-6-2353535, Fax: +886-6-2373149, TW;(2) Department of Dermatology, College of Medicine, National Cheng Kung University, 1 University Rd., Tainan, Taiwan 70101, TW |
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Abstract: | Abstract Previous studies have demonstrated that permeability barrier disruption by acetone treatment significantly enhances skin
permeability to both hydrophilic and amphipathic compounds, but not to highly lipophilic compounds. The purpose of the present
study was to investigate the dependence of permeability on molecular weight (MW) in acetone-disrupted hairless mouse skin
in contrast to normal skin. Penetration of polyethylene glycol (PEG) 300, 600, and 1000 over 12 h was measured using diffusion
cells. High-performance liquid chromatographic methods with refractive index detection were used to separate and quantitate
the individual oligomeric species in the PEG samples. Percutaneous penetration of PEGs exhibited slightly steeper MW dependency
at a transepidermal water loss (TEWL) of 30–41 g/m2 per h in comparison with TEWLs of 0–10 (control skin), 10–20, and 20–30 g/m2 per h, with a higher percentage of smaller oligomer PEGs penetrating than larger ones. Increasing the TEWL of the skin increased
the penetration of all the PEG oligomers, and the degree of the enhancement relative to penetration through control skin increased
with MW and was maximal for oligomers with a MW ranging from 326 to 414 Da. Within the limit of quantitation of the assay,
the MW cut-off for PEG penetration across mouse skin with TEWLs of 0–10, 10–20, and 20–30 g/m2 per h was 414, 590, and 942 Da, respectively, while all the measurable oligomers up to MW 1074 Da were able to penetrate
skin with TEWLs in the range 30–41 g/m2 per h. The results suggest that not only higher amounts but also more varieties of chemicals may penetrate skin with a compromised
barrier than normal skin, implying a higher risk of intoxication and hypersensitization by environmental agents through diseased
skin with impaired barrier function.
Received: 24 October 2000 / Revised: 20 January 2001 / Accepted: 3 March 2001 |
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Keywords: | Polyethylene glycol Molecular weight Percutaneous penetration Permeability barrier disruption Acetone treatment |
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