【摘要】 以人血白蛋白为载体,制备环孢素A白蛋白纳米粒(CyA-HSA),考察其包封率、载药量、粒径、Zeta电位、pH、渗透压、形态、稀释稳定性等理化性质,并以透析法研究其体外释药特性。结果表明,所制得的CyA-HSA纳米粒载药量为14.7%,包封率为85.8%,动态光散射法测定其粒径为240.5 nm,Zeta电位为-32.0 mV,pH为7.0,渗透压为314.7 mOsmol/kg。透射电镜照片表明该纳米体系为规整的球形结构。CyA-HSA纳米制剂比市售环孢素A注射剂(山地明)具有更优越的稀释稳定性,且二者皆具有缓释特性,并呈现零级释药特征。CyA-HSA和山地明注射剂同剂量(7 mg/kg)静脉注射后,二者体内过程均符合二房室模型,与山地明注射剂相比,CyA-HSA的药物清除率和药物从中央室的消除速率常数k10均有显著下降,AUC显著提高(P<0.05)。HSA纳米粒能够高效负载CyA,同时克服了山地明注射剂中增溶剂(聚氧乙烯蓖麻油)的不良反应,有望开发成为环孢素的新一代制剂。更多还原

【Abstract】 Cyclosporine A-loaded human serum albumin nanoparicles(CyA-HSA) were prepared and physicochemical properties including entrapment efficiency,drug-loading capability,particles size,Zeta potential,morphology,pH value and osmotic pressure were evaluated.Dialysis was undertaken to investigate the release of CyA from CyA-HSA nanoparticles in vitro.The obtained CyA-HSA nanoparticles showed spherical shape with mean particle sizes of 240.5 nm and Zeta potential of-32.0 mV.The drug-loading amount and entrapment efficiency were 14.7% and 85.8%,respectively.The pH and osmotic pressure of nanoparticles were 7.0 and 314.7 mOsmol/kg,respectively.CyA-HSA nanoparticles exhibited better dilution stability than commercial cyclosporine A injection,Sandimmune.Both CyA-HSA and Sandimmune exhibited significant sustained release behavior in vitro and both release profiles displayed a zero-order process.The pharmacokinetic study at equal administration dosage(7 mg/kg) in rats showed that cyclosporine A concentration-time data were in accordance with the two-compartment model.The CL and k10 of CyA-HSA significantly decreased and AUC significantly increased compared to those of Sandimmune(P<0.05).CyA-HSA nanoparticles showed obvious solubility enhancement,sustained release and less side effect and toxicity resulting from solubilizing agent of Sandimmune,Cremophor EL,and might be developed as the next generation dosage form of cyclosporine A.更多还原