Systemic and topical drugs for aging skin

Journal of Drugs in Dermatology, August, 2003 by Michael Kockaert, Martino Neumann

Systemic Retinoids

Oral isotretinoin is commonly used in the treatment of acne. In addition to improvement in acne, patients develop smoother, pinker, and lighter skin. One study of patients undergoing rejuvenative procedures compared 60 patients who were treated with oral isotretinoin 10 to 20 mg 3 times a week for 2 months with patients who had not received oral isotretinoin but who had undergone the same rejuvenation procedures. After the study, the patients who had received isotretinoin noted a significant improvement in their photodamage symptoms. However, the risks of teratogenicity and hyperlipidemia are of importance. New studies are needed to compare the effects of topical and oral retinoids (14).

Antioxidants

Free radicals are reactive oxygen species (ROS) formed after physical and/or chemical damage, such as UV radiation. ROS cause oxidative damage to cells as a result of hydroxylation, peroxidation, cross-linking, chain breakage, radical addition to aromatic rings, aldehyde formation, and thiol depletion. ROS damage can be reduced by antioxidants via scavenging, inhibition, and protection. Natural antioxidants include carotenoids, tocopherol (vitamin E), and ascorbic acid (vitamin C).

Tocopherol

The vitamin E complex is a group of 8 compounds known as tocopherols, of which the ? form is the most active (15). This tocopherol is a physical quencher or chemical scavenger of ROS, but can also scavenge free radicals and inhibit auto-oxidation. Tocopherol is a lipophilic, non-enzymatic antioxidant that particularly absorbs the UVB spectrum. Its high lipophilicity makes it well-suited for penetration through the lipid layers of the stratum corneum. As such, tocopherol is able to maintain an intact barrier layer against oxidative damage. Each molecule of tocopherol can provide 2 electrons as antioxidants and thus can scavenge 2 molecules of radical oxygen. In the process, active vitamin E is depleted. To be effective as an antioxidant, tocopherol has to be recycled. Ascorbic acid, glutathione, and coenzyme Q10 recycle tocopherol.

Kondo et al. used cultured skin fibroblasts to demonstrate that tocopherol protects against the cytotoxic effects of UVB irradiation. Dr. Gilchrest's laboratory has also shown that alpha-tocopherol in a liposome preparation has a protective effect on cultured human keratinocytes irradiated with UVB. An animal study on hairless mice showed that topical alpha-tocopherol inhibits thymidine dimer formation due to UVB irradiation in a dose-dependent manner, providing a mechanism through which vitamin E can prevent genetic mutations. Chronic sun damage has been shown to be delayed by application of topical 5% tocopherol before UVB exposure and in vivo studies have shown that topical tocopherol reduces the number of "sunburn cells" that develop in the epidermis as a result of UVB irradiation (15). These studies show that vitamin E is able to limit the proliferation of free radicals and ROS.

Topical formulations such as 5% alpha tocopherol, 5% tocopherol acetate, and 5% tocopherol sorbate have been studied on naked mice after UVB exposure. Tocopherol sorbate reduced the generation of free radicals by 50%, while tocopherol itself increased free radicals, and its acetate form had no effect on free radicals (16). Of interest, tocopherol acetate is the form most commonly used in topical cosmetic preparations. The results of this study may be explained by the low absorption capacity of tocopherol acetate in the UVB spectrum.