The Study Of Resveratrol Emulsomes

As one kind of new drug carrier, emulsomes were studied more in recent years, it is one kind of new dosage form belonging to target-oriented drug delivery system, Emulsomes are a new generation colloidal carrier system in which internal core is made of fats and triglycerides which is stabilized by high concentration of lecithins in the form of o/w emulsion . Emulsomes, having the characteristics of both liposomes and emulsions. By virtue of solidified or semisolidified internal oily core it provides a better opportunity to load lipophilic drugs in high concentration simultaneously a protracted controlled release can also be expected. and the ability to encapsulate water-soluble medicaments in the aqueous compartments of surrounding phospholipid layers. Also, due to their colloidal nature, they can be directly taken up from the blood stream by the macrophages of the liver and spleen after intravenous or intracardiac administration. thus enhances the treatment index, reduces the therapeutic dosage and the toxicity of the drug. Therefore, emulsome acts as a drug delivery system with great potential.Resveratrol is a flavonoid class of small molecule compounds with a wide range of pharmacological effects. Resveratrol can release serum and liver lipids, inhibit the accumulation of lipid peroxides in the liver,and reduced the liver damage. Resveratrol has a good protective effect on cardiovascular disease, it can anti-oxidation, inhibition of platelet aggregation, regulate blood fat, anti-atherosclerosis and coronary heart disease. Studies have shown that resveratrol also has anti-tumor, anti-diabetic activity. Because of high efficacy, low toxicity, resveratrol from the discovery. has been cause for concern.This paper investigates the feasibility of emulsomes as drug delivery system .With resveratrol as a model drug, it examined the effect of preparation methods,formulate and so factors on the encapsulation efficiency of RES emulsome,studied its pharmacokinetic characteristics and tissue distribution after intravenous injection in mice.RES emulsomes were prepared by thin film dispersion(TFD), To prepare a qualified objective for emulsme,optimal formulation of plain RES emulsomes were determined using central composite design.Response variables selected in the research were entrapment efficiency (%),drug loading and OD. the optimized formula was drugs: phospholipids =1:25(weight ration), trilaurin:Lipid=1:30 (weight ratio),cholesterol: phospholipids =1:10 (weight ratio), Tween-80:phospholipids=1:10(weight ratio).The content determination was conducted by HPLC.The results showed: this method has a good linear range and high recovery. It's intra-day and inter-day accuracy of RES were less than 5% microporous membrane filtration was used to determine the encapsulation efficiency of RES emulsome. Through the transmission electron microscopy, the form of emulsome was observed. results showed that the emulsome was intact spherical or oval-shaped ball vesicle, encapsulation efficiency was over 80%.The mean particle diameter was 316.4nm,and Zeta potential was -31.3mv. Emulsomes were preserved at room temperature (29℃-31℃) and 4℃For seven days RES pectively,determine the encapsulation efficiency,leakage rates were 6.1%,4.2% separately,the results showed that the better storage for emulsomes temperature is 4℃.Release behavior in vitro of RES emulsomes was studied and showed sustained-release feature.The pharmacokinetic characteristics of a single dose intravenous injection of RES emulsomes in mice were investigated compared with that of RES solution, and the data were calculated by means of 3p97. According to compartment-model fitting results, RES emulsomes and RES solution were both fitted with two compartment-model.T1/2βof RES emulsomes and solution was 50.17 min min and 19.41 min RES pectively, and the clearance rate was 0.59 ml·min-1 and 1.03 ml·min-1. As the results calculated according to statistical moment theory : AUC of RES emulsomes and solution were 67.29μg·min·ml-1 and 38.76μg·min·ml-1 RES pectively, and MRT were 67.38min and 28.79min. RES emulsomecould prolong the circulation time of drug. Relative exposure (Re) of RES in heart, liver, spleen, lung, kidney was 2.10, 2.16, 1.80, 1.42, 1.34.Targeting efficiency was 0.92, 1.60, 0.94, 0.79, 0.25 and the ratio of maximum concentration was 1.31, 1.18, 0.70, 0.29, 0.43.This indicates that RES emulsome had more higher distribution in liver relatively and improved targeting efficiency. The tissue distribution feature of RES veratrol was C_liver>C_heart>C_spleen>C_lung>C_kidney. resveratrol emulsome has improved drug concentration in heart, liver, spleen, lung, kidney comparing with Resveratrol solution..