The freeze-thawed and freeze-dried stability of cytarabine-encapsulated multivesicular liposomes.

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. 2009 Elsevier B.V. All rights reserved.