Surfaces of skin, barrier

The principle of the TER test is that the test material is applied for up to 24 h to the epidermal surfaces of skin discs taken from the pelts of humanely killed young rats. Corrosive materials are identified by their abUity to produce a loss of normal stratum comeum integrity and barrier function, which is measured as a reduction in the inherent TER below a threshold level (5 kil). Generally, materials that are noncorrosive in animals, but are irritating or nonirritating, do not reduce the TER below the threshold level. A dye-binding step can be incorporated into the test procedure for... 

The dead cells on the surface of skin offer a formidable barrier to drugs. The use of permeation enhancers in controlled delivery patches and techniques such as iontophoresis, electroporation, and ultrasound are applied to enhance the permeation of drugs across skin.131... 

There is substantial history regarding the application of conventional vibrational spectroscopy methods to study the intact surface of skin, the extracted stratum corneum and the ceramide-cholesterol-fatty acid mixtures that constitute the primary lipid components of the barrier. The complexity of the barrier and the multiple phases formed by the interactions of the barrier components have begun to reveal the role of each of these substances in barrier structure and stability. The use of bulk phase IR to monitor lipid phase behavior and protein secondary structures in the epidermis, as well as in stratum corneum models, is also well established 24-28 In addition, in vivo and ex vivo attenuated total reflectance (ATR) techniques have examined the outer layers of skin to probe hydration levels, drug delivery and percutaneous absorption at a macroscopic level.29-32 Both mid-IR and near-IR spectroscopy have been used to differentiate pathological skin samples.33,34 The above studies, and many others too numerous to mention, lend confidence to the fact that the extension to IR imaging will produce useful results. 

Previously13 investigators usually used back or forearm skin for the experiment. It was easier to induce scaly skin on back skin than on forearm skin. In the case of back skin, we stripped SC nine times with adhesive cellophane tape. At that time, the transepidermal water loss (TEWL) value was over 10 mg/cm2/h and most of the SC was removed. In the case of forearm, to induce dry, scaly skin, stripping for 30 to 50 times was needed. One week after treatment, TEWL was higher than the normal level, skin surface conductance decreased, and SC cell area also decreased (Table 10.1). The skin surface became scaly and flaky. Figure 10.1 shows skin surface pictures of the forearm skin with and without barrier disruption. Abnormal scaling is observed on the surface of skin, which was treated with tape stripping. These phenomena are commonly observed in natural dry skin, such as atopic dermatitis and psoriasis. 

Total penetration of the sum of parent compound and metabolite(s) observed with viable skin may be similar to the penetration of the unmetabolized parent compoimd through nonviable skin. The primary barrier to skin absorption is oftrai the nonliving stramm comeum layer on the surface of skin, and metabolism occurs after the rate-limiting step of penetration. The need to maintain viability of skin may be limited to instances when significant biotransformation of test compound in skin occurs. A safety assessment may inaccurately estimate either local or systemic toxicity of a compoimd if it fails to observe significant activation or detoxification of this material in skin. 

The chemical incorporated in a vehicle should reach the surface of the skin at a suitable rate and concentration. If the site of action lies in the deeper layers of the epidermis or below, the substance must cross the stratum comeum, if the skin is intact. Both processes, diffusion from the dosage form and diffusion through the skin barriers, are inextricably linked. They should be considered simultaneously and can be influenced by the choice of formulation. 

Absorption Across the Skin. An aqueous carrier may be used for a variety of dermal products. In fact, carriers can be designed to limit the transportation of the penetration of the active ingredient (such as an insect repellent), if the desired effect is to keep the activity on the surface of the skin. Once again, however, only those materials that are dissolved will be available for penetration across the skin to gain access to the systemic circulation. For almost all chemicals in or about to enter commerce, dermal penetration is a passive process. The relative thickness of the skin makes absorption (into the systemic circulation) slower than the absorption across the GI or pulmonary barriers. This is compounded by the fact that the stratum comeum ftmction is to be impervious to the environment. One of the skin s major functions is protection from infection. Once a chemical penetrates into the dermis, it may partition into the subcutaneous fat. Essentially, absorption across the skin is a two-step process with the first being penetration and deposition into the skin and the second being release from the skin into the systemic circulation. The pattern of blood levels obtained via dermal penetration is generally one with a delayed... 

The chemical barriers are also important but are sometimes neglected in discussions of defence. To some extent they are specific for each tissue or organ and examples are as follows. Enzymes, such as lysozyme, which digests part of the bacterial coat, are present in many secretions (e.g. tears, milk) acid in the stomach, in the vagina, on the surface of the skin alkali in the small intestine mucus in the intestine, respiratory tract and vagina. 

Some evidence indicates that long-term use of topical antimicrobial agents may alter skin flora. Water content, humidity, pH, intracellular lipids, and rates of shedding help retain the protective barrier properties of the skin. When the barrier is compromised (e.g., by hand hygiene practices such as scrubbing), skin dryness, irritation, cracking, and other problems may result. Although the palmar surface of the hand has twice as many cell layers and the cells are >30 times thicker than on the rest of the skin, palms are quite permeable to water. 

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