262 JOURNAL OF COSMETIC SCIENCE 0.0065, log ranks test) in the UV-irradiated mice that received topical vitamin E application. In UV-induced skin damage, an increase in the level of the enzyme orni- thine decarboxylase has been found. Jurkiewicz eta/. (51) examined the antioxidant capabilities of ot-tocopherol and its acetate and sorbate esters using electron paramag- netic resonance in intact mouse skin. They found that topical application of tocopherol sorbate and ot-tocopherol can reduce the number of UV-induced tumors. However, the acetate form did not afford photoprotection. VITAMIN E IN ERYTHEMA AND EDEMA Topical application of ot-tocopherol, [3-carotene, or ascorbate before UV exposure pro- tects murine skin form UVB-induced erythema. Fuchs eta/. (71) analyzed skin after UV exposure and found depletion of tocopherol and ubiquinol. This makes it plausible to suppose that replenishing depleted tocopherol in the skin after UV treatment might have a beneficial effect in reducing UV-induced erythema and skin sensitivity. Rosh- chupkin eta/. (73) studied the effect of ot-tocopherol and ot-tocopheryl acetate when applied before irradiation and 2 min post irradiation. They found ot-tocopherol to greatly inhibit the erythemal response of skin to UV light. However, ot-tocopheryl acetate had almost no antioxidative activity. Potapenko eta/. (74) observed that ot-tocopherol in- hibited the phototoxic effects only if it was present in skin during irradiation. When applied after irradiation, it produced no inhibitory effect. On the other hand, Trevithick eta/. (75) reported that topical application of vitamin E acetate to mouse skin following irradiation significantly reduced the increase in erythema (skin reddening) observed following UVB irradiation, reduced aversive behavior indicative of skin sensitivity, and reduced skin edema measured by magnetic resonance imaging. There was rapid skin healing. It was thought by the authors that topical vitamin E acetate may be useful in treating human sunburn after exposure to UV has occurred. The pure phenolic form of ot-tocopherol was thought to be irritating to the mouse skin when applied topically. Previous work by Poscoe and Reed (76) have indicated that tocopherol esters may be more effective antioxidants than the free phenol, since they can pass the cell membrane and reach some critical intracellular site where they are hydrolyzed to the active phenol form. By contrast, the free ot-tocopherol may be immobilized by the plasma membrane as a result of its lipid solubility and never reach the intracellular site where it is needed. The effect of vitamin E on croton oil dermatitis in rabbits and plaster dermatitis in humans was studied by Kamimura (41). In the former case, swelling and edema was slight and the duration of lesion fairly shortened by the 2% ot-tocopherol application. In the latter case, suppression of irritability (which is the erythema, itching, and dermatitis) was significantly greater in the tocopheryl acetate-added plaster than in the control. The author reasoned that probably vitamin E inhibits histamine liberation from granules of mast cells and serotonin liberation from inside the tissue cells. Interestingly, low-dose dietary vitamin E (0.2%) did not provide protection against mercury arc lamp-induced erythema in mice. Skin bioavailability may be insufficient at this systemic concentration to afford any photoprotection. Topical use of vitamin E has been recommended for the treatment of a widespread disseminated form of granuloma anulare, which is resistant to all kinds of other treat- ment modalities. An explanation for its efficacy is the potential of vitamin E as an antioxidant and free-radical scavenger, which may play a role in the pathogenesis of

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