Stratum corneum symmetry breaking : the polarity for permeability
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Presented by: Tsuyoshi Ikeda
【Introduction】
The skin is the largest organ in the human body and plays an important role in maintaining homeostasis by separating the internal environment from the external environment. Particularly, the stratum corneum (SC), as the outermost layer of the skin, is in direct contact with the external environment and performs a barrier function for protecting the human body from excessive water loss and invasion of foreign substances.
On the other hand, the topical base and active agent including cosmetics applied to the skin are required to permeate and diffuse into the SC, and furthermore, need to be distributed to the epidermis layer through the SC. Therefore, the SC needs to have a certain degree of skin permeability. It is conceivable that there is a trade-off relation between the barrier function and the permeability of the SC.
The SC layer is thought to have a structural polarity (asymmetry) in the upper SC (outside) and lower SC (inside), because the corneocytes forming the SC layer is flattened and enlarged with keratinization (turnover). The presence of polarity (direction) for permeability related to the inside-out and outside-in barrier function is, however, not clear.
We hypothesized that there is a polarity between inside-out and outside-in permeability in the SC in order to achieve both of improvement in skin permeability and enhancement of barrier function, and tried to clarify the function of the SC.
【Method】
To investigate where there is difference between the inside-out and outside-in permeability of the SC, a permeability test of water and of sodium fluorescein (SF, M.W.: 376) as a highly water-soluble model drug was performed using a normal abdominal human SC resected during plastic surgery and Franz diffusion cells. Further, comprehensive analysis of molecule localization in the SC was performed with Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS).
【Result】
It was confirmed that the permeability of water and SF from the lower SC (inside-out barrier model) was more suppressed than that from the upper SC (outside-in barrier model). Further, the results of TOF-SIMS showed that the expression of cholesterol and fatty acids derived from intercellular lipid or sebum was higher at the lower SC side, confirming their uneven distribution in the SC.
【Discussion and Conclusion】
Our study suggests that the SC layer has a polarity in its permeability in which the SC does not easily let out water which is the most important in vivo substance, while the in vivo permeation of water and low molecular weight materials from external environment is confirmed. Further, from the TOF-SIMS analysis, the presence of uneven distribution of the molecules in the SC was confirmed. Based on the results, it is suggested that the SC may strategically achieve the spatial inside-out and outside-in barrier function by forming structural change through keratinization (turnover) and creating the polarity (asymmetry) for the inside-out and outside-in permeability, i.e., 'symmetry breaking'. This clarification of the function of the SC could lead to a breakthrough in the development of cosmetics that both enhance barrier function and improve in skin permeability.
The skin is the largest organ in the human body and plays an important role in maintaining homeostasis by separating the internal environment from the external environment. Particularly, the stratum corneum (SC), as the outermost layer of the skin, is in direct contact with the external environment and performs a barrier function for protecting the human body from excessive water loss and invasion of foreign substances.
On the other hand, the topical base and active agent including cosmetics applied to the skin are required to permeate and diffuse into the SC, and furthermore, need to be distributed to the epidermis layer through the SC. Therefore, the SC needs to have a certain degree of skin permeability. It is conceivable that there is a trade-off relation between the barrier function and the permeability of the SC.
The SC layer is thought to have a structural polarity (asymmetry) in the upper SC (outside) and lower SC (inside), because the corneocytes forming the SC layer is flattened and enlarged with keratinization (turnover). The presence of polarity (direction) for permeability related to the inside-out and outside-in barrier function is, however, not clear.
We hypothesized that there is a polarity between inside-out and outside-in permeability in the SC in order to achieve both of improvement in skin permeability and enhancement of barrier function, and tried to clarify the function of the SC.
【Method】
To investigate where there is difference between the inside-out and outside-in permeability of the SC, a permeability test of water and of sodium fluorescein (SF, M.W.: 376) as a highly water-soluble model drug was performed using a normal abdominal human SC resected during plastic surgery and Franz diffusion cells. Further, comprehensive analysis of molecule localization in the SC was performed with Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS).
【Result】
It was confirmed that the permeability of water and SF from the lower SC (inside-out barrier model) was more suppressed than that from the upper SC (outside-in barrier model). Further, the results of TOF-SIMS showed that the expression of cholesterol and fatty acids derived from intercellular lipid or sebum was higher at the lower SC side, confirming their uneven distribution in the SC.
【Discussion and Conclusion】
Our study suggests that the SC layer has a polarity in its permeability in which the SC does not easily let out water which is the most important in vivo substance, while the in vivo permeation of water and low molecular weight materials from external environment is confirmed. Further, from the TOF-SIMS analysis, the presence of uneven distribution of the molecules in the SC was confirmed. Based on the results, it is suggested that the SC may strategically achieve the spatial inside-out and outside-in barrier function by forming structural change through keratinization (turnover) and creating the polarity (asymmetry) for the inside-out and outside-in permeability, i.e., 'symmetry breaking'. This clarification of the function of the SC could lead to a breakthrough in the development of cosmetics that both enhance barrier function and improve in skin permeability.