Physicochemical and pharmacological characterization of alpha-tocopherol-loaded nano-emulsion system.
The main purpose of the present study is to develop a novel nano-emulsion (NE) formulation of alpha-tocopherol (alpha-TC) with enhanced oral bioavailability and pharmacological effects. Three NE formulations of alpha-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 400nm, in proportion to the amount of loaded alpha-TC. Although all NE formulations of alpha-TC were found to be negatively charged with the zeta-potential of ca -40mV, NE formulations at alpha-TC content of 30% or higher exhibited severe aggregation of droplets in NE formulations during long-term storage. After oral administration of 10% alpha-TC-loaded NE formulation (30mg alpha-TC/kg) in rats, higher alpha-TC exposure was observed with a 2.6-fold increase of bioavailability as compared to the control mixture of oil and alpha-TC. In streptozotocin-induced diabetic rats, oral administration of the alpha-TC-loaded NE formulation (30mg alpha-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 alpha-TC.
Hatanaka
Junya
J
Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Chikamori
Hina
H
Sato
Hideyuki
H
Uchida
Shinya
S
Debari
Kazuhiro
K
Onoue
Satomi
S
Yamada
Shizuo
S
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004655:Emulsions; D008027:Light; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry*; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012542:Scattering, Radiation; D013678:Technology, Pharmaceutical / Q000379:methods; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D000975:Antioxidants; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D024502:alpha-Tocopherol