Drug delivery and in vivo efficacy of resveratrol from nano/submicron encapsulated formulations

• Main Authors: Liao Mei-Hui, 廖美惠
• Other Authors: Fang Jia You
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/76707393528908017956

碩士 === 長庚大學 === 天然藥物研究所 === 93 === Resveratrol is a naturally occurring phytoalexin found in grape, which has preventing properties in coronary heart disease. To overcome the disadvantage of high elimination in oral administration and poor solubility in application, we introduced resveratrol in three different lipid emulsions vesicles with nano- or submicron-size for increasing solubility of drug and in vivo efficacy in an injectable way. The first formulation in the present study was multiple systems of lipid emulsions with liposomes made by coconut oil, soybean lecithin, glycerol formal, and non-ionic surfactant. The second formulation employed vitamin E in the oil components of the lipid emulsions system so called tocol emulsions. In the third formulation, perflouropentane gases were intrapped with coconut oil and soybean lecithin made lipid emulsion to be activated with ultrasound so called lipid-coated microbubbles. The sizes of these systems was ranged from 52 to 579 nm and decreased in the order of lipid-coated microbubbles > lipid emulsions > tocol emulsions. Lipid-coated microbubbles showed the highest drug entrapment ratio nearly 90%. The inclusion of Brij 98 and Brij 35 in lipid emulsions and tocol emulsions reduced the release rate of resveratrol and showed the good stability in thermo incubation. Adding Pluronic F-68 in lipid-coated microbubbles showed different tendency in drug release rate depend on the ratio of oil components. Treated with ultrasound significantly increased the drug released from lipid-coated microbubbles in the present of plasma. The safety of these formulations was evaluated by hemolytic experiments. Intraperitoneal injection of resveratrol entrapped in lipid emulsions and tocol emulsions dramatically decreased the vascular neointima formation after arterial injury, but not significant in the animals treated with lipid-coated microbubbles due to the unsuitable administration way.