Department of Pharmaceutics, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, PR China.
Int J Pharm. 2010 Mar 15;387(1-2):147-53. doi: 10.1016/j.ijpharm.2009.12.017. Epub 2009 Dec 18.
To investigate the stability of cytarabine-encapsulated multivesicular liposomes (MVLs) following freeze-thawing/freeze-drying, three types of phospholipids (EPC, DPPC, and DOPC) were separately employed to prepare MVLs using a double emulsification method. The cytarabine retention (CR), phase transition behavior, aggregation/rupture of vesicles and particle size were monitored using HPLC, differential scanning calorimetry (DSC), digital biological microscopy and a laser diffraction particle size analyzer. The effect of trehalose, the lipid bilayer composition and triglyceride on the drug retention was also investigated. The DPPC-MVLs and EPC-MVLs achieved the best protective effect during freeze-thawing and freeze-drying, respectively, while DOPC-MVLs produced the lowest drug retention during both procedures. Digital biological microscopy showed that most of the MVLs were divided into small irregular and regular vesicles after freeze-thawing and freeze-drying, which was in agreement with the reduction in particle size. The vesicle fragmentations may result from the splitting of triglyceride from the lipid membrane or rupture of the lipid membrane. The rehydrated EPC-MVLs still displayed a controlled-release profile in vitro, and the results presented in this work should help in stabilizing hydrophilic drug-encapsulated liposomes with a large particle size.
为了研究阿糖胞苷包封的多室脂质体（MVL）在冻融/冷冻干燥后的稳定性，分别使用两种乳化方法使用三种磷脂（EPC、DPPC 和 DOPC）来制备 MVL。使用 HPLC、差示扫描量热法（DSC）、数字生物显微镜和激光衍射粒度分析仪监测阿糖胞苷保留率（CR）、相变行为、囊泡聚集/破裂和粒径。还研究了海藻糖、脂质双层组成和甘油三酯对药物保留的影响。在冻融和冷冻干燥过程中，DPPC-MVL 和 EPC-MVL 分别达到了最佳的保护效果，而 DOPC-MVL 在这两种过程中产生的药物保留率最低。数字生物显微镜显示，大多数 MVL 在冻融和冷冻干燥后分裂成小的不规则和规则的囊泡，这与粒径的减小一致。囊泡的破裂可能是由于甘油三酯从脂质膜中分离或脂质膜破裂所致。复水后的 EPC-MVL 仍在体外显示出控制释放的特性，本工作的结果应该有助于稳定粒径较大的亲水性药物包封脂质体。
