Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd U3092, Storrs, Connecticut, 06269, USA.
Pharm Res. 2014 Jan;31(1):97-103. doi: 10.1007/s11095-013-1135-z. Epub 2013 Jul 24.
Freeze-thaw cycling is an important processing step in the preparation of liposomes that leads to the encapsulation of drug molecules. There is considerable variability in the number of freeze-thaw cycles reported in the literature. This work is designed to aid in liposomal formulation design by gaining an insight into the drug encapsulation process and an understanding of liposome stabilization during various thawing conditions.
The effects of different thawing temperatures, as well as "annealing" at subzero temperatures on a liposome formulation, are reported here.
Two freeze-anneal-thaw (FANNT) cycles (freezing to -196°C, annealing at -1.4°C for ~30 min, thawing at 65°C) resulted in the maximum predicted encapsulation efficiency without causing any significant change in particle size or zeta potential. Annealing at -22°C was shown to be destabilizing due to limited hydration of the liposomes in the frozen state.
It was shown that two important processes are occurring during the FANNT cycling that affect liposome encapsulation efficiency. The first is drug diffusion in the frozen state and the second is fusion/destabilization of the liposomes. This is the first report on the annealing of liposomes and understanding the mechanism of drug encapsulation using the freeze-thaw cycling method.
冻融循环是制备脂质体的一个重要处理步骤，可导致药物分子的包封。文献中报道的冻融循环次数有相当大的差异。这项工作旨在通过深入了解药物包封过程以及在各种解冻条件下对脂质体的稳定作用，来帮助脂质体制剂的设计。
本文报道了不同解冻温度以及在亚低温下“退火”对脂质体制剂的影响。
两次冻融-退火-解冻（FANNT）循环（冷冻至-196°C，在-1.4°C 下退火约 30 分钟，在 65°C 下解冻）导致了最大的预测包封效率，而不会导致粒径或 Zeta 电位发生任何显著变化。在-22°C 下退火由于冷冻状态下脂质体的水合作用有限而被证明是不稳定的。
研究表明，在 FANNT 循环过程中发生了两个重要的过程，这两个过程会影响脂质体的包封效率。第一个是药物在冷冻状态下的扩散，第二个是脂质体的融合/失稳。这是首次报道关于脂质体退火的内容，以及使用冻融循环方法了解药物包封的机制。
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