环孢素A白蛋白纳米粒的制备、体外释放及大鼠药代动力学评价  

Cyclosporine A-loaded albumin nanoparticles:preparation,in vitro release and evaluation of pharmacokinetics in rats

作　　者：张勇[1] 高敏姣[1] 张来芳[1] 霍美蓉[2] 彭晓玲[2] 周建平[2] 

机构地区：[1]江苏正大天晴药业股份有限公司,南京210023 [2]中国药科大学药剂学教研室,南京210009

出　　处：《中国药科大学学报》2013年第3期239-243,共5页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81102397);国家"重大新药创制"科技重大专项资助项目(No.2009ZX09310-004)~~

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。Cyclosporine A-loaded human serum albumin nanoparicles （CyA-HSA） were prepared and physico- chemical properties including entrapment efficiency, drug-loading capability, particles size, Zeta potential, mor- phology, 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 inV. 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 com- pared to those of Sandimmune（ P 〈 0.05）. CyA-HSA nanoparticles showed obvious solubility enhancement, sus- tained 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.

关 键 词：环孢素A 白蛋白 纳米粒 药代动力学 

分 类 号：R96[医药卫生—药理学]