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.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
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)~~
关键词
环孢素A
白蛋白
纳米粒
药代动力学
cyclosporine A
albumin
nanoparticles
pharmacokinetics
