Transdermal Delivery of Paclitaxel-Anionic Nanoparticles to Epidermis Layer, Pterostilbene, and Pterostilbene glycoside, and Their Application for Treatment of Skin Cancer and Wrinkle

Composite nanoparticles, “anionic bicelles”, composed of anionic phospholipid of 1,2- dipalmitoyl- sn-glycero-3-phosphorylglycerol (DPPG) and paclitaxel were prepared by mixing them in water and a subsequent heating/cooling/ultrasonicating process. Anionic DPPG-paclitaxel nanoparticles (particle size: 12 nm) could be prepared after ultrasonic fragmentation at low temperature of 4°C. Upon addition of fluorescently labeled paclitaxel nanoparticles stabilized with DPPG to rat skin tissue (in vitro), the nanoparticles “anionic bicelles” (particle size: 12 nm) infiltrated into the epidermis layer penetrating stratum corneum (intercellular space: ca. 100 nm). In addition, during the anti-skin cancer test using mouse model of skin cancer, our study revealed that the numbers of papillomas of the mouse applied with paclitaxel nanoparticles stabilized with DPPG, “anionic bicelles”, to mouse skin were decreased, although those of the mouse applied with paclitaxel itself to mouse skin (control) were increased. Thus, this study established that since paclitaxel nanoparticles stabilized with DPPG could permeate stratum corneum and be incorporated into the epidermis layer of mouse, they could also treat skin cancer (in vivo). On the other hand, a mixture of anionic phospholipids, sodium cholate and Technol PG, allowed for formation of anionic nanoparticles, “anionic liposomes”, (particle size: 3 nm). This study established that as pterostilbene and pterostilbene glycoside could permeate stratum corneum and be incorporated into the epidermis layer, they could also treat wrinkle.