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SATURDAYOctober 16SESSION 32:30– 2:50Click here to return to Dermatology Update 2004 Schedule and Abstracts |
Sheldon R. Pinnell New methods of photoprotection are needed to curb the epidemic of skin cancer – an epidemic worsened by an aging population, ever-increasing outdoor activities and escalating immunosuppression related to medical treatments. Sunscreens are not the complete answer. Recent studies point out that in actual usage individuals apply only 20-25% the amount used to determine SPF values. Since SPF is an exponential function, actual protection is no more than three to fourfold at this level of application for any sunscreen. Moreover, the best sunscreens available only protect against 55% of free radicals generated in skin by ultraviolet irradiation. The skin naturally protects itself from the sun with antioxidants. These include vitamin C in fluids and vitamin E in stratum corneum and membranes. My research laboratory is interested in developing antioxidant formulations that can be applied to skin to increase the natural reservoir and provide additional photoprotection. Since antioxidants are naturally unstable compounds, they provide challenges for formulation. To work, they must be chemically stable, they must get into skin, and they must be used at meaningful concentrations. Finally, they must be effective at providing photoprotection. L-ascorbic acid (vitamin C) can be used topically, but proper formulation is crucial. It must be at a pH below 3.5 in order to enter skin. It is maximally effective for increasing skin levels at a concentration of 20%. Skin can be saturated in 3 days, and following saturation, half life of removal is about 4 days. It is effective for protecting the skin against UVB and UVA and can protect against UV-immunosuppression. Alpha tocopherol (vitamin E) can enter skin when applied topically. Maximal percutaneous absorption occurs at 1% concentration. Alpha tocopherol is effective for protecting skin against photoinjury, photocarcinogenesis and UV-immunosuppression. Because vitamin C and vitamin E are relatively unstable in topical formulations, derivatives (esters) have been synthesized to improve stability. Vitamin C derivatives include ascorbyl palmitate and magnesium ascorbyl phosphate. Vitamin E derivatives include tocopherol acetate. These derivatives must then be converted in tissue, back to the vitamin to be effective. These derivatives are successfully converted in the stomach when used in vitamin pills, but not readily converted when used topically for skin protection. In the human body, antioxidants function as an interactive network, with chemical reconstitution of antioxidants after they are oxidized during protective functions. As a network they work synergistically. Vitamin C and vitamin E, when formulated together at maximal concentrations for percutaneous absorption, provide synergistic photoprotection for skin when applied topically. We have recently discovered that ferulic acid provides added chemical stability to a solution of vitamin C and vitamin E. When heated at 45ºC for one month, vitamin E is 100% stable and vitamin C is more than 90% stable. Ferulic acid is a ubiquitous plant antioxidant and is also used in making plant cell walls. A solution of 15% L-ascorbic acid, 1% alpha tocopherol and 0.5% ferulic acid provides eight- to ten-fold protection against solar-simulated irradiation of skin. Protection is demonstrated for erythema, sunburn cell formation, caspase-3 and caspase-7 activation and thymine dimer formation. Thymine dimers are critical DNA mutations intimately involved in skin cancer formation. In summary, topical vitamins C and E stabilized with ferulic acid provide synergistic photoprotection for skin and prevent thymine dimer formation. Derivatives of vitamins C and E are not readily converted to free vitamins when used topically. Reference List
Click here to return to Dermatology Update 2004 Schedule and Abstracts |