Perspectives on Assessment of Risks from Dermal Exposure to Polycyclic Aromatic Hydrocarbons
Rhoda G. M. Wang, James B. Knaak, Howard I. Maibach in Health Risk Assessment, 2017
In contrast, less than 50% of radioactivity in the culture medium from viable skin slices was extractable into ethyl acetate. In the organic extract from the culture medium of viable human skin, 18% of total radioactivity was found in BaP, and all major classes of BaP metabolites were identified (BaP diols, other polar BaP metabolites, BaP phenols and BaP quinones) (Kao et al., 1985). Digestion of nonviable human skin slices following topical application of [C]BaP revealed that 87% of the radioactivity remained in parent compound, whereas in digests of viable human skin only 57% remained in BaP and the rest was attributed to BaP metabolites (Kao et al., 1985). Similar observations were made in experiments using skin from other species. From the media of rat, mouse, and marmoset skin preparations, approximately 70% of the radioactivity remained in aqueous fractions following extraction with ethyl acetate. Chromatographic analysis showed that all major classes of BaP metabolites were present. BaP diols and polar metabolites predominated. Metabolism of chemicals during cutaneous passage may represent a general phenomenon (Bronaugh et al., 1989). Factors that affect the percutaneous absorption of chemicals have been reviewed (Wester and Maibach, 1983). Skin can be described most simply in terms of three basic layers, the epidermis, the dermis, and the subcutaneous fat (Wester and Maibach, 1983). The stratum corneum is the outermost layer of the epidermis, and is composed of dead, inactive cells. The stratum corneum is the principal barrier to absorption of most chemicals and materials with which the skin comes into contact. Below the stratum corneum lies the epidermis. Data indicate that the epidermal layer contains most of the drug-metabolizing enzymes and is the most metabolically active skin layer. The epidermis contains a complete complement of drug-metabolizing enzymes, including a cytochrome P-450 mixed function oxygenase system. These enzymes in skin are inducible as they are in liver. Enzyme activities have been compared in skin and liver (Wester and Maibach, 1983). Cutaneous enzyme activities are usually reported based on enzyme activities in whole skin homogenates, and have traditionally been considered to be lower than hepatic activities. However, most of the enzyme activity in skin is localized to the epidermis, and the epidermis comprises only 2.5 to 3% of the total skin volume. Using epidermal volume to calculate the metabolic activity of skin, the skin appears to be from 80 to 240% as active a drug-metabolizing organ as liver (Wester and Maibach, 1983). Chemicals that penetrate the stratum corneum into the epidermis may be subject to metabolic activities equal to or greater than those found in liver due to a concentration effect.
Dermatotoxicology of the vulva
Miranda A. Farage, Howard I. Maibach in The Vulva, 2017
The vulva has unique skin properties that may predispose it to increased irritation and dermatitis. Embryologic developmental differences contribute to the distinct qualities of vulvar skin. The vulvar mucosa is nonkeratinized, originating from the embryonic endoderm, whereas the keratinized cutaneous epithelia of the surrounding mons pubis, labia, and clitoris, is derived from the embryonic ectoderm (5,6). The vulva is subject to increased water loss and permeability to water, suggesting that vulvar skin is a less complete barrier and is more prone to adversely react to certain irritants. The stratum corneum functions to retain water for the skin. The vulvar skin stratum corneum is thinner than other parts of the body, measuring 0.02 μm compared to 11.2 μm on the forearm, supporting the idea of its decreased barrier function. The vulva’s increased water loss, and thus permeability to water, is shown objectively by transepidermal water loss (TEWL) measurements by an evaporimeter. Mean TEWL in the vulva is higher at 1.42 × 10 g/m/h compared to the lower measure of 8.68 × 10 g/m/h in the forearm (7). However, in other circumstances, the vulva skin has been observed to better adapt than forearm skin to other irritants, such as menses blood (8). Hence, it is important to recall that the unique vulvar skin can show itself to be more or less prone to irritation in different situations. The amount of skin surface water loss is subject to more “bursts” (or varied increases) in the vulvar skin versus forearm skin. This varied water loss may be affected by occlusion and eccrine sweating on the vulvar skin, as in vulvar skin folds occluding on itself or garment occlusion. This variation can lead to data assessment complications in vulvar skin irritation studies (9). Researchers have tried to control the occlusion factor on the vulva by drying out (via a desiccation chamber to absorb evaporated water) and comparing the capacitance (measure of skin hydration) of vulvar and forearm skin, as measured by a capacitometer. Differences in TEWL and capacitance between forearm and dried vulvar skin were lessened but still apparent, suggesting that occlusion alone does not explain the vulvar skin’s higher TEWL and that there are biological differences inherent in the vulva (10).
Role of Vitamin C in Chronic Wound Healing
Qi Chen, Margreet C.M. Vissers in Vitamin C, 2020
The skin is composed of two main layers—the outermost epidermis and the underlying dermis, with the differing structures of the two layers clearly reflecting their distinct functions. The epidermis is a stratified squamous epithelium predominantly made up of keratinocytes. The keratinocytes closest to the dermis, termed the basal cells, divide, and cells move outward toward the surface, differentiating as they do so (Figure 9.1). During differentiation, keratinocytes lose almost all of their organelles and much of their cytoplasm, they increase production of specialized structural proteins, their cell membrane is replaced by a cellular envelope of cross-linked proteins, and they secrete lipids [2,3]. These changes allow the formation of the outermost epidermal layer, the stratum corneum, which consists of flattened, metabolically inactive cells, now termed corneocytes, sealed together with lipid-rich intercellular domains forming a nearly water-impermeable barrier (Figure 9.1). The stratum corneum interacts with the external environment and fulfills almost all of the physical barrier function of the skin [4]. The epidermis is continually renewing; it takes 30–60 days for new keratinocytes to reach the skin surface [1]. In comparison, the thicker dermal layer consists mainly of a complex extracellular matrix that provides strength and flexibility and gives structural support to the epidermis. It is also home to the vascular, lymphatic, and neuronal systems of the skin. The dermis is relatively acellular (Figure 9.1). Fibroblasts are the main cell type present and are responsible for synthesizing many components of the extracellular matrix [5]. The majority of the dermis is composed of collagen fibers that account for 70%–80% of its dry weight. They are arranged in bundles in a random basket-weave pattern and provide the tensile strength of the skin, preventing it from tearing when stretched. Elastin fibers are also present in the dermis, although they are much less abundant than collagen. Elastin provides the skin with recoil or resilience, allowing it to return to an unstretched state. Both of these fibers are embedded into a proteoglycan matrix that, in conjunction with polymeric hyaluronic acid, is crucial for maintaining skin hydration, lubricating between collagen and elastic fiber networks during skin movement, and providing resistance to compression [1].
Dry skin management: practical approach in light of latest research on skin structure and function
Published in Journal of Dermatological Treatment, 2020
Ehrhardt Proksch, Enzo Berardesca, Laurent Misery, Johan Engblom, Joke Bouwstra
Dry skin is a common condition that is attributed to a lack of water in the stratum corneum. With the availability of new technologies, light has been shed on the pathophysiology of dry skin at the molecular level. With the aim to discuss implications of this latest research for the optimal formulation of emollients designed to treat dry skin, five specialists met in November 2017. Research on three topics thereby provided particularly detailed new insights on how to manage dry skin: research on the lipid composition and organization of the stratum corneum, research on natural moisturizing factors, and research on the peripheral nervous system. There was consensus that latest research expands the rationale to include physiological lipids in an emollient used for dry skin, as they were found to be essential for an adequate composition and organization in the stratum corneum but are reduced in dry skin. Latest findings also confirmed the incorporation of carefully selected humectants into a topical emollient for dry skin, given the reduced activity of enzymes involved in the synthesis of moisturizing factors when skin is dry. Overall, the group of specialists concluded that the previous concept of the five components for an ideal emollient for dry skin is well in accordance with latest research.
Numerical simulation of iontophoresis in the drug delivery system
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2016
Nenad Filipovic, Marko Zivanovic, Andrej Savic, Goran Bijelic
The architecture and composition of stratum corneum act as barriers and limit the diffusion of most drug molecules and ions. Much effort has been made to overcome this barrier and it can be seen that iontophoresis has shown a good effect. Iontophoresis represents the application of low electrical potential to increase the transport of drugs into and across the skin or tissue. Iontophoresis is a noninvasive drug delivery system, and therefore, it is a useful alternative to drug transportation by injection. In this study, we present a numerical model and effects of electrical potential on the drug diffusion in the buccal tissue and the stratum corneum. The initial numerical results are in good comparison with experimental observation. We demonstrate that the application of an applied voltage can greatly improve the efficacy of localized drug delivery as compared to diffusion alone.
Effect of esters based on terpenoids and GABA on fluidity of phospholipid membranes
Published in Journal of Liposome Research, 2019
Mariia Nesterkina, Sergii Smola, Iryna Kravchenko
The influence of esters based on gamma-aminobutyric acid (GABA) and mono-/bicyclic terpenoids on membrane structure was investigated. The mechanism of action for terpenoid esters on phospholipids of artificial membranes and lipids isolated from the rat stratum corneum was studied by fluorescence and FT-IR spectroscopy. We report here, that inclusion of monocyclic terpenoid esters in phospholipid liposomes leads to growth of excimer to monomer ratio (IE/IM) indicating a decrease of membrane microviscosity. Another mechanism of influence on biomembranes was proposed for ester of bicyclic borneol - in this case a high ratio of vibronic peak intensities (I1/I3) was revealed. The addition of terpenoid esters appears in the FT-IR spectra as intensity reduction of absorption bands associated with C = O, P = O and P–O–С groups of lecithin phospholipids. Similar results were obtained after esters addition to lipids isolated from stratum corneum indicating a decrease of hydrogen bonds number between polar groups of lipids. Thus, the influence of terpenoid esters on molecular organization of the lipid matrix substantiates the feasibility of their use after transdermal delivery in vivo.