SKIN DELIVERY OF VITAMIN E 263 granuloma anulare and tissue damage (77,78). The application of a 0.1-5% solution of o•-tocopherol in ethanol can also inhibit UV-induced skin edema in a dose-dependent fashion (79). However, Fisher (80) reports three types of allergic eruptions from topical vitamin E, namely delayed eczematous, immediate urticarial, and erythema-multiforme- like. Pure o•-tocopherol and concentrated topical preparations (10-20%) can irritate human skin (37). SKIN PHOTOAGING The premature aging of skin is mediated by prolonged exposure to UV light and results from damage to collagen. The firmness, texture, or tone of the skin is maintained by the integrity of the elastic fiber and collagen in the dermal connective tissue. Wrinkles often result from a loss of subcutaneous fat, degeneration of collagen fibers in the connective tissue, and fragmentation of elastic fibers. A late change in photoaging is a substantial loss of collagen as it is replaced by the masses of elastosis. UVA causes primarily dermal damage, leading to photoaging with elastosis, wrinkling, and loss of skin elasticity (81). Singlet oxygen is implicated in UVA-mediated stimulation of matrix proteinases, which are thought to be involved in cutaneous photoaging (82). Although most of the UVB is absorbed in the epidermis, some UVB may contribute to dermal photoaging via matrix proteinase activation (83). The usefulness of vitamin E in maintenance of the connective tissue is confirmed. Photoprotective sunscreen formulations composed of 5% tocopherol in ethanol can reduce the wrinkling and sagging associated with photoaging (84). Vitamin E deficiency promotes UV-induced lipid peroxidation and accelerates the cross-linking of collagen in skin and subcutaneous tissue (85). Vitamin E also has an important protective role against serious light-induced conditions of the eye like cataractogenesis and retinal photodeterioration (86). Photoaging differs from intrinsic aging. Photoaging results in deeper wrinkles and furrows at the skin surface and a greater frequency of precancerous cells, and the dermal microcirculation is badly damaged. A sensitive area of the face like the eyelids was used to compare vitamin E cream along with a placebo. o•-Tocopherol induced smoothing of fine lines and wrinkles (32). Jurkiewicz et aL (51), using a mouse model of photoaging, studied the effect of o•-tocopherol, o•-tocopheryl acetate, and sorbate esters on UVB radiation-induced skin wrinkling. o•-Tocopheryl acetate did not provide significant protection against skin wrinkling at 15 weeks into the study. Both o•-tocopherol sorbate and o•-tocopherol were highly photoprotective against UV-induced photoaging. In addition, tocopherol sorbate treatment decreased baseline radical forma- tion in skin, suggesting a possible anti-aging role in sunscreen formulations. SKIN SMOOTHNESS, SKIN SOFTENING, AND SKIN HYDRATION Studying the skin's surface topography has been used as an indication of the degree of hydration as well as an interpretation of smoothness and softness. Dry, rough, or dam- aged skin manifests as "scruffy" appearance, with discontinuities in the lines, decreased distance between lines, and an irregular appearance. Hydrated skin has comparatively wider lines with a more regular appearance and is less sharply demarcated. In an in vivo skin softening study conducted for Hoffman-La Roche Inc., Yeung (87) used soaps containing 0.5% and 1.0% vitamin E acetate for 15 days. The treated groups showed a

264 JOURNAL OF COSMETIC SCIENCE substantial skin-softening effect as compared to those using conventional soaps without vitamin E acetate. He found the skin-softening effect to be cumulative. Tamburic et (88) studied both the short-term and long-term moisturizing potential of a cosmetic o/w emulsion containing 5 % d-o•-tocopherol on healthy human volunteers. The capacitance- measuring method was used to evaluate changes in skin surface hydration. They found that d-o•-tocopherol in the concentration of 5% w/w did increase the moisturizing potential of a topically applied product when used on a long-term basis. On a short-term basis, however, no significant difference was found in the performance of the placebo and active emulsion, and the effect of o•-tocopherol was thought to be predominantly oc- clusive. ACNE VULGARIS Vitamin E combinations are thought to be directed toward certain pathophysiological characteristics of acne vulgaris. Oral administration of vitamin A and vitamin E to over a hundred patients at an average daily dose of 100,000 IU of vitamin A and 800 IU of vitamin E successfully controlled acne vulgaris with no untoward side effects. No antibiotics were necessary (89-91). This treatment was thought to correct the defects in keratinization due to dysfunction of the sebaceous follicles, thus preventing the forma- tion of milia (whiteheads) and comedones (black heads), depriving the Propio,ibacteri•m ac, es of adequate culture medium. Vitamin E also prevented irritating lipid peroxidation of sebum, damaged by bacterial growth, which is responsible for the inflammatory aspects of acne. MISCELLANEOUS Vitamin E has been indicated for the treatment of various skin diseases, alopecia, and periodontal disease. Williams eta/. (92) observed a marked improvement in nails treated with topical 5 % vitamin E solution in dimethyl sulfoxide to increase nail growth rates in yellow nail syndrome. Goldsmith (93) studied the effect of vitamin E on severe chronic thread fungus of the toenail (onychomycosis) and found a dramatic improve- ment. PERCUTANEOUS ABSORPTION OF VITAMIN E Skin delivery of an active ingredient from a topical formulation depends on its release and passive diffusion through the stratum corneum. In principle, this diffusion obeys Fick's law. If, for the purposes of simplification, it is assumed that the horny layer is a homogenous diffusion barrier, then according to Fick's law the penetration rate after steady state has been reached depends upon the concentration of the active ingredient in the vehicle, the mobility of the active ingredient (diffusion coefficient), and the inter- action of the active ingredient with the vehicle and the skin (distribution coefficient) (94). The penetration rate J is given as J = (K x D x C)/h (Eq. 3) where h is the thickness of the horny layer, D is the diffusion coefficient, c is the vehicle concentration, and K the distribution coefficient. The penetration properties of a for-