载环孢素纳米球的制备及释放特性*

目的：制备一种环孢素A（CsA）缓释纳米体系。方法：以PLA-co-PEG共聚物材料作为环孢素药物的释放载体；采用超声振荡技术制备载环孢素的PLA—PEG—PLA纳米球；分析纳米球的粒径与分布以及纳米球降解过程中的形貌变化；体外释放试验探讨制备的纳米球的降解特性以及与载体材料、介质pH值之间的影响关系；小鼠灌胃后HPLC法测定血药浓度。结果：采用PLA—PEG—PLA共聚材料装载CsA，药物包封率达到89．2％。纳米球平均粒径为242．3nm，载药后平均粒径增大到320．2nm。扫描电镜分析发现纳米球在磷酸缓冲液中溶胀程度与降解速率依赖于介质pH值。体外模拟释放表明载药纳米球的药物释放速率与载体降解速率一致，持续稳定释药时间〉7d。动物模型也证实该载CsA纳米球可维持血液中稳定的药物浓度5d以上。结论：利用本方法制备的载CsA纳米球是一种较理想的环孢素药物剂型，具有临床应用价值。

Preparation and release properties of cyclosporine A nanospheres

Objective:To prepare sustained release cyclosporine A(CsA) nanospheres.Methods:Using PLA-PEG-PLA copolymers as the carrier matrix,the polymers nanospheres of CsA were prepared by emulsification and sonication technology.The diameters and size distribution of nanospheres were analyzed by laser scattering analysis.The surface modality of nanospheres during the degradation of the CsA nanospheres was studied by scanning electron microscopy(SEM).The degradable features in vitro and the correlationship of the carrier matrix to pH environment for the release rate of the CsA nanospheres were assessed using a dissolution test in vitro.A RP-HPLC system was used to assay the CsA concentration in blood samples of the mice.Results: The CsA nonospheres had an enveloping efficiency of 89.2% and the average diameter of 242.3 nm for free nanospheres and 320.2 nm for CsA-loaded nanospheres.The SEM analysis showed that the swelling rate and degradation rate of the nanospheres were dependent on the pH environment of PBS medium.The dissolution test in vitro concluded that the sustained release rate remained the same as the degradable rate of the CsA nanospheres,producing a relatively flat,sustained CsA concentration for 7 d in vitro.The plasma CsA concentration released from the nanospheres in vivo remained stable for 5 d.Conclusion:The CsA nanospheres offered an optimally sustained release of CsA.