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KMID : 0984920080100020019
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Journal of Skin Barrier Research
2008 Volume.10 No. 2 p.19 ~ p.25
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Physiological influences on drug transport across human stratum corneum in vivo
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Tsai Jui-Chen
Sheu Hamm-Ming
Lin Ming-Kai
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Abstract
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This paper discusses the influences of physiological factors including anatomical sites and sebum secretion on drug transport across human stratum corneum (SC) in vivo by utilizing noninvasive, quantitative attenuated-total-reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) technology. 4-Cyanophenol (CP) and cimetidine (CM) were selected as two model compounds of different lipophilicity and molecular size. To investigate regional variation, saturated solutions of CP and CM were applied to the skin surface of Chinese males, at five anatomical sites, including forearm, back, thigh, leg, and abdomen, followed by sequential tape-stripping of SC. The drug concentration profiles in the tape-stripped SC were determined using ATR-FTIR spectroscopy. Thickness of the SC was estimated simultaneously using twopoint
measurements of transepidermal water loss before and after completion of tape stripping. Estimation of partition, diffusion and permeability coefficients was achieved by analysis of the data using the unsteady-state diffusion equation. The results demonstrated the rank order of regional variation in permeability coefficients was similar for both drugs and decreased in the order of back > forearm > thigh > leg ≥ abdomen, but the variation was more prominent for CM. Regional variation in SC transport of CP was mainly influenced by its intrinsic diffusivity across the SC, whereas variation in transport of CM could be attributed to both thermodynamic and kinetic differences among different anatomical skin sites. Similar methodology was applied to study the effects of sebum on SC drug transport. We found that sebum supplement increased the SC permeability of CM at the forearm for more than three fold, but not that of CP. The increase in SC permeability of CM was mainly attributed to the enhanced SC diffusivity. Sebum removal at the forehead has small, but significant effect on the SC permeability of CM. SC permeability of CM was linearly correlated to the frequency shift of CH2
asymmetric/symmetric stretching in the ATR-FTIR spectra of the SC due to sebum treatment. Sebum treatment increased the SC permeability of relatively hydrophilic drug and altered the barrier function of stratum corneum by disordering structures of the intercellular lipid molecules.
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KEYWORD
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stratum corneum, cyanophenol, cimetidine, permeability, physiological factors
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