环孢素A硬脂酸纳米球的实验研究

目的：探讨硬脂酸纳米球作为新型药物载体的可能性。方法：制备了硬脂酸纳米球(SA-NP)，用电镜考察其形态，测定了各种理化特性；以环孢素A(CYA)为模型药物，制备了环孢素A硬脂酸纳米球(CYA-SA-NP)；对其进行了红外光谱测定和差示扫描量热分析；建立了测定CYA-SA-NP和血中CYA的HPLC法。以市售CYA微乳型口服液为对照，测定了口服CYA-SA-NP在大鼠体内的药代动力学参数和相对生物利用度。结果：CYA-SA-NP的平均粒径为316.6nm，CYA的平均包封率为88.39%，CYA和硬脂酸之间无化学反应发生；CYA-SA-NP的相对生物利用度接近80%，而且达峰时间较晚，具有明显的缓释效果。结论：硬脂酸纳米球将可能成为一种新型的药物载体。

STUDIES ON THE CYCLOSPORIN A LOADED STEARIC ACID NANOPARTICLES

AIM: To investigate the possibility of SANP (stearic acid nanoparticles) as a new kind of drug carrier. METHODS: SANP was prepared by melthomogenization. Some of its physicochemical properties were investigated. Its morphology was examined by transmission electron microscope. Cyclosporin A (CyA), as a model drug was then encapsulated into SANP (CyASANP). Following the establishment of HPLC method for CyA in CyASANP or blood samples, the encapsulation ratio of CyA to SANP was estimated, and pharmacokinetics as well as bioavailability of CyASANP after po administration to Wistar rats were studied, using Sandimmun Neoral (an available microemulsion system of CyA) as a control. RESULTS: The mean diameter of CyASANP was 3161 nm, while the encapsulation ratio of CyA to SANP reached to 8836%. It was demonstrated by IR spectra and differential scanning calorimetry that no chemical reaction occurred between the CyA and SA. The relative bioavailability of CyASANP over control was nearly 80%, and the time reach maximum concentration (Tmax) of CYA after po administration of CYASANP was significantly delayed than the control, suggesting an obvious sustained release effect. CONCLUSION: SANP might be a very potential drug carrier.