Natural moisturizing factors (NMFs) play an important role in maintaining the physical properties of the stratum corneum (SC). The relationship between SC water content and NMFs has long been investigated. Recently, we demonstrated that potassium lactate as an NMF increased SC water content more than sodium lactate did. The details of the moisturizing mechanism of NMFs, however, were not revealed. We, therefore, investigated the cause of the SC moisturizing effect of potassium lactate in comparison with sodium lactate. Using differential scanning calorimetry, we found that potassium lactate increased the bound water content of plantar SC more than what sodium lactate did. We also found, however, that the bound water content of the potassium lactate solution was less than that of the sodium lactate solution, suggesting that potassium lactate increased the water molecules interacting with SC components. Moreover, potassium lactate increased the ratio of hydrogen ⁄ deuterium exchange at 1340 ⁄ cm, which represents the OH bending mode, of plantar SC spectra obtained by the attenuated total reflectance infrared spectroscopy. We assign this band to the OH group of the serine residue. These results suggest that potassium lactate increases the water-holding capacity of the SC by increasing interaction between water molecules and the OH group of serine in SC keratin.

) was measured and correlated with the physicochemical properties of the esters, including their solubility, viscosity, wettability, surface tension, and uptake. The amount of each model compound that permeated through the silicone membrane was not significantly correlated with the solubility of the esters but was significantly correlated with all other measured physical properties of the esters. Similar correlations were observed for the amounts of AMP, BA, and FP that passed through the Strat-M ® membrane. However, the amount of CF that permeated through the Strat-M ® membrane also correlated with the solubility of the esters. There was a highly significant correlation between the amount permeating through the silicone and Strat-M ® membranes because the model compounds had high lipophilicity. These findings demonstrated that to control the permeation of various chemicals through artificial membranes, it is important to consider the uptake of the esters and that the solubility of the esters is also an important consideration when using a more complex membrane.Key words alternative membrane; high-throughput; ester; silicone membrane; Strat-M; physical property In order to develop transdermal drug delivery systems, permeability has been evaluated using Fick's law of diffusion. 1,2)Fick's First Law indicates that the rate of mass transfer across a membrane is proportional to the concentration gradient expressed across the membrane. Synthetic artificial membranes are uniform and are designed to mimic human skin to avoid variability among tissues. They offer a simple and reproducible alternative to human and animal skins and provide key information to help understand the mechanisms of drug permeation by the evaluation of changes in a basic permeation parameter because, theoretically, skin permeation of chemicals can be expressed by physicochemical phenomena of diffusion and partition of compounds. Therefore, synthetic artificial membranes have been used in permeability evaluations. [3][4][5] Maitani et al.6) evaluated the permeability of diclofenac salts and free diclofenac acid through a silicone membrane to understand the mechanism of percutaneous absorption of ionizable drugs, and the existence of the lipid pathway for diclofenac salts was the same as for diclofenac acid. Strat-M ® is a commercially available multi-layered artificial membrane that is made from polyether sulfonic acid. 7) We reported previously also that the permeability coefficients, partition parameters, and diffusion parameters of chemicals through a Strat-M ® membrane were similar to those in human skin, and those in silicone membrane were under-or over-estimation to those in human skin, depending on the lipophilicity of the model compounds. 8,9) In addition, several previous studies have assessed the effects of vehicles on the permeation of chemicals through artificial membranes.10-13) For example, Twist and Zatz 10)evaluated the effect of alcohol on the permeation rate (flux) of methyl-, ethyl-, propyl-, and butyl-parabens. Dias et al. 12)r...

We evaluated the effectiveness of a silicone membrane as an alternative to human skin using the skin permeation parameters of chemical compounds. An in vitro permeation study using 15 model compounds was conducted, and permeation parameters comprising permeability coefficient (P), diffusion parameter (DL 2 ), and partition parameter (KL) were calculated from each permeation profile. Significant correlations were obtained in log P, log DL 2 , and log KL values between the silicone membrane and human skin. DL 2 values of model compounds, except flurbiprofen, in the silicone membrane were independent of the lipophilicity of the model compounds and were 100-fold higher than those in human skin. For antipyrine and caffeine, which are hydrophilic, KL values in the silicone membrane were 100-fold lower than those in human skin, and P values, calculated as the product of a DL 2 and KL, were similar. For lipophilic compounds, such as nbutyl paraben and flurbiprofen, KL values for silicone were similar to or 10-fold higher than those in human skin, and P values for silicone were 100-fold higher than those in human skin. Furthermore, for amphiphilic compounds with log K o/w values from 0.5 to 3.5, KL values in the silicone membrane were 10-fold lower than those in human skin, and P values for silicone were 10-fold higher than those in human skin. The silicone membrane was useful as a human skin alternative in an in vitro skin permeation study. However, depending on the lipophilicity of the model compounds, some parameters may be over-or underestimated.Key words silicone membrane; skin; membrane permeation; alternative membrane Skin forms an interface between the body and environment and functions as a firm barrier against undesirable elements. Many skin permeation studies of therapeutic drugs have been conducted to develop transdermal drug delivery systems (TDDSs) for the purpose of preventing the hepatic first-pass effect, which is observed for some oral dosage forms, and for controlling release over long periods of time.1-3) For the development and evaluation of TDDSs, in vitro skin permeation tests using excised human skin have been performed in the European Union (EU) and United States; however, in Japan, it is difficult to obtain human skin, so permeation studies using human skin are not performed as frequently. Therefore, animal skins, particularly those of hairless rat, mouse, and guinea pig, have been used for the evaluation of percutaneous absorption. Recently, however, sales of cosmetics in the EU, 4) for which animal experiments were performed during their development have been prohibited out of concern for animal welfare, and alternative membranes are now required to determine percutaneous absorption. In addition, permeation studies using animal or human skin are associated with several difficulties and limitations for assessing the effects of formulations components, because of the complex nature of this biological tissue and inter- and intra-individuality of skin.Artificial model membranes offer a simple and ...

Regulation of hyaluronan (HA) is important for the maintenance of epidermal homeostasis. Here we examined the mechanism by which 1-ethyl-β-N-acetylglucosaminide (β-NAG2), a newly developed N-acetylglucosamine (NAG) derivative, increases HA production in cultured human epidermal keratinocytes. When keratinocytes were treated with β-NAG2, mRNA expression of HA synthase 3, which is responsible for HA production in human keratinocytes, was not influenced, but the intracellular level of UDP-NAG, a substrate used for HA synthesis, was increased. By using a synthetic substrate for β-N-acetylglucosaminidase (β-NAGase), keratinocytes were found to possess β-NAGase activity, and treatment of o-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc), an inhibitor of β-NAGase, abolished the release of NAG from β-NAG2 in keratinocytes. Furthermore, PUGNAc attenuated the β-NAG2-induced intracellular UDP-NAG and HA production in keratinocytes. These results suggest that β-NAG2 is converted to NAG by endogenous β-NAGase in keratinocytes, and the resulting NAG is further metabolized to UDP-NAG and utilized for HA production.