Atopic dermatitis (AD) is a chronic inflammatory skin disease, occurring most commonly during early infancy and childhood. The skin of an AD patient is susceptible to environmental allergens and becomes red, flaky and itchy.1) Recent progress in pathogenesis has revealed that AD is associated with abnormal immunological responses. Cytokines including interleukin (IL)-4 and IL-5 activate mast cells and eosinophils, and can result in elevated levels of immunoglobulin E (IgE).2) Furthermore, inflammation-related enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are pivotal for provoking the inflammatory response in dermatitis.3,4) Even though corticosteroids have so far been widely used for the treatment of AD, longterm administration of steroidal drugs is very restricted due to severe side effects. 5) Less toxic natural compounds are being sought as new potential anti-AD agents.
6)Oregonin (ORG) is a diarylheptanoid derivative, (5S)-1,7-bis-(3,4-dihydroxyphenyl)-heptane-3-one-5-O-beta-D-xylopyranoside, isolated from the bark of Alnus japonica.7) Various biological activities of ORG including an anti-oxidative effect, 8) inhibitory effects on nitric oxide synthesis and COX-2 expression, 9,10) and an immunomodulatory effect 11) have been reported. Recently, it has been further investigated as a natural remedy for the treatment of autoimmune diseases, including AD. On topical applications of ORG, it has to be delivered to the relevant skin layers of the epidermis and dermis. However, the skin permeation of ORG to the deeper dermal layer is very limited because of its hydrophilicity. Although a partially disturbed barrier in AD can favor drug permeation through the skin, an efficient delivery system is still the main concern for the development of topical preparations.
12)Liposomes have been widely introduced as a non-toxic nanocarrier which can encapsulate both polar and nonpolar compounds. They usually promote skin permeation of a drug by intact vesicular skin penetration, a penetration enhancing effect, or penetration of liposomes through the transappendageal route. 13,14) Elastic liposomes (EL), consisting of phospholipids and an edge activator are one of the novel liquid-state vesicles for topical delivery of drugs. In comparison to conventional liposomes (CL), EL are generally able to respond to an external stress by rapid shape transformation and penetrate the skin efficiently in terms of quantity and depth.15,16) Furthermore, since liposomal vesicles composed of alternating lipid and water phases are structurally similar to the skin constitution, the application of liposomes moisturizes the skin and reduces the irritation resulted from allergic skin disorders.17) It has been reported that addition of Tat (Trans-activating transcriptional activator) peptide would facilitate the skin penetration and transportation of drug into immune cells. 18,19) This short peptide demonstrated the efficiency of translocation of the various molecular cargos with no apparent toxicity.
20)In this...
