9-硝基喜树碱复合磷脂隐形脂质体的制备工艺研究
Study on Preparation of 9-Nitrocamptothecin Stealth Liposomes Composed of DPPC and SPC
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摘要: 目的 考察9-硝基喜树碱（9-nitrocamptothecin， 9-NC）复合磷脂隐形脂质体的制备方法与工艺，并进一步比较了经隐形修饰对9-NC复合磷脂脂质体的药剂学性质的影响。方法 建立了采用滤膜法测定9-NC脂质体包封率的方法， 并以包封率为评价指标，考察了9-NC复合磷脂隐形脂质体的制备方法并优化了制备工艺参数。然后以未经隐形修饰的9-NC复合磷脂脂质体为对照，进一步考察了包封率、粒径、多分散系数、Zeta电位、内酯稳定性等药剂学性质。结果 采用薄膜-超声法制备9-NC复合磷脂隐形脂质体包封率高于乙醇注入法，进一步考察得到其优化的工艺参数为复合磷脂摩尔比例HSPC∶SPC=1∶9（摩尔比），成膜时间与压力分别为100 min与0.095 MPa。隐形修饰对9-NC复合磷脂脂质体的包封率（80%以上）影响不大，同时也不会影响其表面电位，但经隐形修饰后粒径显著减小，内酯稳定性显著增加。结论 采用最优方法与工艺制备的9-NC复合磷脂隐形脂质体包封率高，载药效果能够满足体内研究的需要；隐形修饰有利于提高9-NC复合磷脂脂质体的内酯稳定性。Abstract: OBJECTIVE To investigate the preparing methods and process of 9-nitrocamptothecin (9-NC) stealth liposomes composed of HSPC and SPC and to compare the pharmaceutical properties between 9-NC liposomes and 9-NC stealth liposomes. METHODS Encapsulation efficiency determination method for 9-NC stealth liposomes was established by ultrafiltration membrane method. The preparation for 9-NC stealth stealth liposomes was carefully studied and the process parameters were optimized. Furthermore， compared with 9-NC liposomes composed of HSPC and SPC without stealth-modified， encapsulation efficiency， particle size， zeta potential and polydispersity lactone stability were investigated. RESULTS The encapsulation efficiency of 9-NC stealth liposomes preparation by film-ultrasonic method was significantly improved， compared to those by ethanol injection method， and the optimized process parameters were HSPC:SPC=1:9. The formation time was 100min and formation pressure was 0.095 Mpa. Though there was on influence on the exception of encapsulation efficiency （80%） and zeta potential， particle size and lactone stability were significantly optimized by modified stealth materials. CONCLUSION Samples prepared by optimized method and process obtained high encapsulation efficiency and met the needs of drug effects in vivo studies; modified stealth materials may have effect in enhancing Lactone stability of 9-NC stealth liposomes composed of HSPC and SPC.
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