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

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 albumin nanoparticles:preparation, in vitro release and evaluation of pharmacokinetics in rats

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.