【摘要】 目的:以N-辛基-O,N-羟乙基壳聚糖(OGC)为载体材料,制备环孢素-壳聚糖胶束(CsA-OGC),并对其理化性质及其大鼠口服相对生物利用度进行研究。方法:以载药量和包封率为主要指标,对CsA-OGC的制备工艺进行优选,动态光散射法测定其粒径、Zeta电位,透射电镜观察其形态,并考察其稳定性。将市售制剂Neoral及CsA-OGC按7 mg·kg-1大鼠口服,HPLC法测定全血药物浓度,WinNonlin 5.1计算药动学参数。结果:透析法工艺为最佳制备工艺,载药量和包封率分别为29.5%和75.3%,粒径为185.2 nm,透射电镜照片表明载药胶束为规整球形结构,且具有良好的稀释稳定性。与市售制剂Ne-oral相比,CsA-OGC胶束口服给药在大鼠体内的Cmax和AUC均显著提高(P<0.05),相对生物利用度为137.0%。结论:OGC胶束具优越的载药性能,且对药物具有良好的促吸收效果,作为口服药物载体具有优良的应用前景。更多还原

【Abstract】 OBJECTIVE To prepare cyclosporine A-loaded amphiphilic chitosan micelles(CsA-OGC),and to determinate physicochemical properties of the micelles and oral bioavailability in rats.METHODS The preparation method of CsA-OGC was optimized using drug loading content(DL,wt%) and encapsulation efficacy(EE,%) as target indexes.The size and Zeta potential were determined by dynamic light scattering(DLS) technique.The shape of the particles was observed using transmission electron microscopy(TEM) imaging.The stability of the formulation was also evaluated.After oral administrated with commercial Neoral and CsA-OGC formulation at the dose of 7 mg·kg-1 into rats,the drug concentration in blood was determined by HPLC method,and the pharmacokinetic parameters were calculated by WinNonlin 5.1.RESULTS Dialysis method was the best method for preparing CsA-OGC micelles with DL and EE of 29.5% and 75.3%,respectively.The particle size of CsA-OGC micelles was 185.2 nm with regular spherical shape observed from TEM images.Compared with Neoral,a commercial CsA formulation,CsA-OGC micelles achieved a significant increase in both Cmax and AUC after oral administrated in rats(P<0.05),the calculated relative bioavailability was 137.0%.CONCLUSION OGC micells presented excellent drug loading capability and enhanced drug absorption in some extent and showed promising perspectives when served as drug carrier for oral delivery.更多还原