Physicochemical and pharmacological characterization of a-tocopherol-loaded nano-emulsion system

• Published in: International journal of pharmaceutics Vol. 396; no. 1-2; pp. 188 - 193
• Main Authors: Hatanaka, Junya, Chikamori, Hina, Sato, Hideyuki, Uchida, Shinya, Debari, Kazuhiro, Onoue, Satomi, Yamada, Shizuo
• Format: Journal Article
• Language: English
• Published: 30.08.2010
• ISSN: 0378-5173
• DOI: 10.1016/j.ijpharm.2010.06.017

The main purpose of the present study is to develop a novel nano-emulsion (NE) formulation of a-tocopherol (a-TC) with enhanced oral bioavailability and pharmacological effects. Three NE formulations of a-TC at different loading amounts (10%, 30% and 50%) were prepared by a mechanochemical method. Physicochemical properties of NE formulations were characterized with a focus on the morphology by transmission electron microscopy (TEM), droplet size distribution and zeta-potential by dynamic light scattering (DLS), and long-term stability. According to the TEM images and DLS data, mean diameters of NE droplets ranged from 80 to 400 nm, in proportion to the amount of loaded a-TC. Although all NE formulations of a-TC were found to be negatively charged with the zeta-potential of ca -40 mV, NE formulations at a-TC content of 30% or higher exhibited severe aggregation of droplets in NE formulations during long-term storage. After oral administration of 10% a-TC-loaded NE formulation (30 mg a-TC/kg) in rats, higher a-TC exposure was observed with a 2.6-fold increase of bioavailability as compared to the control mixture of oil and a-TC. In streptozotocin-induced diabetic rats, oral administration of the a-TC-loaded NE formulation (30 mg a-TC/kg) exhibited a significant reduction of lipoperoxidant in several organs, especially the liver; however, the control mixture was less effective. With these findings, the NE approach might be efficacious to improve the oral bioavailability and anti-oxidative activities of a-TC.