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.
Int J Pharm. 2010 Aug 30;396(1-2):188-93. doi: 10.1016/j.ijpharm.2010.06.017. Epub 2010 Jun 15.
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.
本研究的主要目的是开发一种新型的α-生育酚（α-TC）纳米乳（NE）制剂，以提高其口服生物利用度和药理作用。采用机械化学法制备了三种不同载药量（10%、30%和 50%）的α-TC NE 制剂。重点考察了制剂的形态学特性，采用透射电子显微镜（TEM）观察形态，采用动态光散射（DLS）法测定粒径分布和zeta 电位，考察了制剂的长期稳定性。根据 TEM 图像和 DLS 数据，NE 液滴的平均直径范围为 80-400nm，与载药量呈正相关。尽管所有载有 α-TC 的 NE 制剂均带负电荷，zeta 电位约为-40mV，但当载药量为 30%或更高时，NE 制剂在长期储存过程中会出现液滴严重聚集。在大鼠口服 10%载有 α-TC 的 NE 制剂（30mg α-TC/kg）后，与对照油和 α-TC 混合物相比，α-TC 的暴露量增加了 2.6 倍，生物利用度提高。在链脲佐菌素诱导的糖尿病大鼠中，口服载有 α-TC 的 NE 制剂（30mg α-TC/kg）可显著降低几个器官，尤其是肝脏中的脂质过氧化产物；然而，对照混合物的效果较差。有这些发现，NE 方法可能有效提高 α-TC 的口服生物利用度和抗氧化活性。
