Superoxide dismutase (SOD) is a potent antioxidant agent that protects against UV-induced skin damage. However, its high molecular weight is a significant obstacle for efficient delivery into the skin through the stratum corneum and development of antioxidant activity. Recently, we developed a non-invasive transfollicular delivery system for macromolecules using a combination of liposomes and iontophoresis, that represents promising technology for enhancing transdermal administration of charged drugs (IJP, 403, 2011, Kajimoto et al.). In this study, in rats we attempted to apply this system to intradermal delivery of SOD for preventing UV-induced skin injury. SOD encapsulating in cationic liposomes was subjected to anodal iontophoresis. After iontophoretic treatment, the liposomes were diffused widely in the viable skin layer around hair follicles. In contrast, passive diffusion failed to transport liposomes efficiently into the skin. Iontophoretic delivery of liposomes encapsulating SOD caused a marked decrease in the production of oxidative products, such as malondialdehyde, hexanoyl lysine, and 8-hydroxi-2-deoxyguanosine, in UV-irradiated skin. These findings suggested that functional SOD can be delivered into the skin using a combination of iontophoresis and a liposomal system. In conclusion, we succeeded in developing an efficient intradermal SOD delivery system, that would be useful for delivery of other macromolecules.
Key words superoxide dismutase; iontophoresis; liposome; transfollicular delivery; antioxidant activityThe skin is exposed constitutively to ultraviolet (UV) rays that cause the production of reactive oxygen species (ROS) in the skin, resulting in diverse skin disorders.1) It is well-known that the classes of UV that reach the ground are UVA and UVB. UVA readily penetrates deep layers of the skin, and causes production of melanin and wrinkling associated with destruction of collagen fiber, resulting in aging of the skin.
1)UVB causes skin inflammation and DNA damage that contribute to the pathogenesis of serious skin disorders, such as skin malignancy.1) ROS are also involved in the development of skin damage, and therefore elimination of ROS is essential for protecting the skin from UV-induced damage.Superoxide dismutase (SOD) may be used to prevent and treat ROS-induced disorders of various tissues as it has potent antioxidant activity.2) Because of its poor pharmacokinetic profile, systemic administration of free SOD does not result in induction of efficient in vivo antioxidant activity.3) In contrast, the skin is an available site for topical application of SOD due to its accessibility. Percutaneous delivery of SOD is therefore considered to be a promising method for prophylaxis or therapy of UV-induced skin damage. However, SOD are highly hydrophilic macromolecules and do not readily penetrate the deeper layers of the skin as the outer layer of the skin, the stratum corneum, functions as a significant barrier prohibiting penetration of drug molecules larger than 500 Da.
4)Iontophoresis...