Untitled

Abstract

Penetration of various compounds through shed snake skin was measured in vitro to examine the effect of lipophilicity and molecular size of a compound on permeability through this model membrane. The permeabilities were found to be controlled by the lipophilicity and the molecular size of the permeant. The smaller and the more lipophilic the compound, the greater the permeability. Equations have been developed to predict the permeability from the molecular weight and the distribution coefficient of a compound. Further, the lipophilicity of shed snake skin is similar to that of human skin and the response of shed snake skin to the molecular size of a permeant is more similar to human skin than to hairless mouse skin. Considering the similarities between shed snake skin and human stratum corneum in terms of structure, composition, and permeability characteristics, the same considerations may apply to permeability through human stratum corneum.

Dermal Peptide Delivery Using Enhancer Molecules and Colloidal Carrier Systems – Part IV: Search for an Alternative Model Membrane for Future ATR Permeation Studies Using PKEK as the Model Substance

“…Since the availability of human skin is limited, the aim of these experiments was to find a suitable, easily accessible alternative. In various publications, skin of the domestic pig and snake, among others, was used [10-15]. In a review, the differences in permeability and lag time between human and pig skin, for instance, from various studies were examined.…”

“…During this process, it is stretched and is about 20–25% longer than the snake itself [16]. The shed skin is pure nonliving epidermis (SC) with no hair follicles [15]. It consists of three layers: (1) the outer β-layer, rich in β-keratin; (2) the α-keratin- and lipid-rich intermediate mesos layer; and (3) the inner α-layer, rich in α-keratin.…”

“…The lipid composition of human skin and snake skin is very similar: neutral lipids are the main constituent, and fatty acids with chain lengths of C16 and C18 have been found [14, 18]. Itoh et al [15] already showed that the permeability of different molecules is often similar between snake skin and human skin, although often lower in snake skin. This makes snake skin a better model membrane than other animal skins, since most hides have a higher permeability than human skin due to large numbers of hair follicles.…”

“…It has been shown in various publications that their anatomical and biochemical properties are very similar [13, 20-23]. The dermis of pigs and humans consists of elastic and collagenous fiber bundles [15, 20]. The SC has a similar thickness: 13–15 μm in humans [2, 14, 24] and 21–26 μm in pigs [2, 21].…”

Estimation of Maximum Transdermal Flux of Nonionized Xenobiotics from Basic Physicochemical Determinants

“…In this equation, “a” stands for a coefficient accounting for the difference in the drug solubilities in SC lipids and bulk octanol, and usually is found to be in the range of 0.7 – 0.9 indicating a somewhat more hydrophilic nature of the anisotropic SC lipids as compared to the isotropic bulk octanol 11, 13, 14, 17 . Additionally, the diffusivity of a drug molecule in the SC lipid domain (D) can be linked to its size through an inverse power function 29, 30 or a free volume theory 21, 31–33 . In the free-volume theory, molecular volume is habitually substituted with MW for simplicity and without loss of prediction accuracy e.g.…”