| Amphiphilic block copolymer is widely researched as a kind of drug carrier,because it can be spontaneously formed micelle with nano-size and regularly core-shell type sphere in shape in aqueous solution. amphiphilic block copolymer(ABC)is synthesized with hydrophilic chain and lyophobic chain,and can be synthesized with specified chemical constitution or molecular weight copolymer;it can be formed ordered aggregation—micell by the way of association reaction in the solution under the condition of being lower than critical micell concentration.Because micelll owns small particle diameter,it can generate unique distribution in vivo. Universally if the particle diameter is under 100nm,the micelle can be avoided from phagocytosis of RES, decreasing damage of liver and kidney and toxity of drug; because its core-shell type owns high carried drug rate,it can increase retented time of hydrosoluble drug, obtaining the effect of delayed release and long circle;and increase the dissolubility of insolubled drug elevating bioavailability. Particle diameter-small polymer micelle own good tissue permeability, especially in leaky tissues (Tissue of tumor, Inflammation or infarct area)because it doesn't easily be phagocytized by macrophages, extending the time in vivo,—enhanced permeability and retention (EPR); so it has the function of native passive target. It is very suitable to be considered as ideal carrier of insoluble antineoplastic drug.The topic put quercetin as model drug,choose poly(ε-caprolactone)-b-poly(ethylenelycol)-b-poly(ε-caprolactone) (PCEC) triblock copolymers as drug carrier material, and prepare quercetin poly(ε-caprolactone)-b-poly(ethylenelycol)-b-poly(ε-caprolactone) (PCEC) triblock copolymers micelle. We investigated the effect of preparation methods, various Molecular Weight copolymers ,formulae and so on factors on the encapsulation efficiency of quercetin micelle, studied its leakage rate, hemolytic and pharmacokinetic characteristics after intravenous injection in rats. Quercetin micelle were prepared by thin film dispersion method .the optimized formula was drug2mg,PCEC40mg and PBS(Ph=6)2ml.The content determination was conducted by HPLC. Filter membrane method was used to determine the encapsulation efficiency of quercetin micelle. Through the transmission electron microscopy, it is formed with core-shell type sphere in shape in aqueous solution.After comparing the phenomena of test tubes with negative and positive control, quercetin micelle were found not to cause hemolysis in-vitro. Micells were preserved at room temperature (29℃to 31℃) and 4℃for seven days respectively ,determine the encapsulation efficiency, leakage rates were 28.3%,5.8%separately, the results showed that the better storage for micell , temperature is 4℃.The pharmacokinetic characteristics of a single dose intravenous injection of quercetin micelle in rats were investigated compared with that of quercetin solution, and the data were calculated by means of 3p97. According to compartment-model fitting results, quercetin micelle and quercetin solution were both fitted with two compartment-model with a weight of 1. T1/2βof quercetin micelle and solution was 40.28±2.53min and 9.15±4.91min respectively, and the clearance rate was 0.10±0.04ml·min-1 and 0.04±0.01ml·min-1. As the results calculated according to statistical moment theory; AUC of quercetin micelle and solution was 84.7±23.62μg·min·ml-1and 36.55±18.47μg·min·ml-1 respectively, and MRT was 29.19±0.34min and 6.27±0.06min. Many pharmacokinetic parameters showed significant difference(P<0.05).
|
PDF Full Text Request