Department of Pharmaceutical Technology, Friedrich Schiller University Jena, Jena, Germany.
J Liposome Res. 2012 Mar;22(1):31-41. doi: 10.3109/08982104.2011.584319. Epub 2011 Jun 20.
A new strategy for fast, convenient high-throughput screening of liposomal formulations was developed, utilizing the automation of the so-called ethanol-injection method. This strategy was illustrated by the preparation and screening of the liposomal formulation library of a potent second-generation photosensitizer, temoporfin. Numerous liposomal formulations were efficiently prepared using a pipetting robot, followed by automated size characterization, using a dynamic light scattering plate reader. Incorporation efficiency of temoporfin and zeta potential were also detected in selected cases. To optimize the formulation, different parameters were investigated, including lipid types, lipid concentration in injected ethanol, ratio of ethanol to aqueous solution, ratio of drug to lipid, and the addition of functional phospholipid. Step-by-step small liposomes were prepared with high incorporation efficiency. At last, an optimized formulation was obtained for each lipid in the following condition: 36.4 mg·mL(-1) lipid, 13.1 mg·mL(-1) mPEG(2000)-DSPE, and 1:4 ethanol:buffer ratio. These liposomes were unilamellar spheres, with a diameter of approximately 50 nm, and were very stable for over 20 weeks. The results illustrate this approach to be promising for fast high-throughput screening of liposomal formulations.
开发了一种新的策略，用于快速、方便地进行高通量脂质体制剂筛选，该策略利用了所谓的乙醇注入方法的自动化。通过制备和筛选第二代光敏剂替莫泊芬的脂质体制剂文库来说明该策略。使用移液机器人高效地制备了许多脂质体制剂，然后使用动态光散射板读数器自动进行粒径表征。在某些情况下还检测了替莫泊芬的包封效率和 ζ 电位。为了优化配方，研究了不同的参数，包括脂质类型、注入乙醇中的脂质浓度、乙醇与水溶液的比例、药物与脂质的比例以及功能性磷脂的添加。采用逐步添加的方法制备了具有高包封效率的小单层脂质体。最后，在以下条件下为每种脂质获得了优化的配方：脂质 36.4mg·mL(-1)，mPEG(2000)-DSPE 13.1mg·mL(-1)，乙醇：缓冲液比为 1:4。这些脂质体为单室球体，直径约为 50nm，在超过 20 周的时间内非常稳定。结果表明，该方法有望用于快速高通量脂质体制剂筛选。
