Division of Pharmaceutical Biosciences, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Division of Pharmaceutical Biosciences, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
J Control Release. 2018 Aug 28;284:213-223. doi: 10.1016/j.jconrel.2018.06.029. Epub 2018 Jun 28.
Light triggered drug delivery systems offer attractive possibilities for sophisticated therapy, providing both temporal and spatial control of drug release. We have developed light triggered liposomes with clinically approved indocyanine green (ICG) as the light sensitizing compound. Amphiphilic ICG can be localized in different compartments of the liposomes, but the effect of its presence, on both triggered release and long term stability, has not been studied. In this work, we report that ICG localization has a significant effect on the properties of the liposomes. Polyethylene glycol (PEG) coating of the liposomes leads to binding and stabilization of the ICG molecules on the surface of the lipid bilayer. This formulation showed both good storage stability in buffer solution (at +4-37 °C) and adequate stability in serum and vitreous (at +37 °C). The combination of ICG within the lipid bilayer and PEG coating lead to poor stability at elevated temperatures of +22 °C and + 37 °C. The mechanisms of the increased instability due to ICG insertion in the lipid bilayer was elucidated with molecular dynamics simulations. Significant PEG insertion into the bilayer was induced in the presence of ICG in the lipid bilayer. Finally, feasibility of freeze-drying as a long term storage method for the ICG liposomes was demonstrated. Overall, this is the first detailed study on the interactions of lipid bilayer, light sensitizer (ICG) and PEG coating on the liposome stability. The localization of the light triggering agent significantly alters the structure of the liposomes and it is important to consider these aspects in triggered drug delivery system design.
光触发药物递送系统为复杂的治疗提供了有吸引力的可能性，为药物释放提供了时间和空间控制。我们已经开发了用光敏化化合物临床批准的吲哚菁绿（ICG）触发的脂质体。两亲性 ICG 可以定位于脂质体的不同隔室中，但它的存在对触发释放和长期稳定性的影响尚未研究。在这项工作中，我们报告说 ICG 的定位对脂质体的性质有显著影响。脂质体的聚乙二醇（PEG）涂层导致 ICG 分子在脂质双层表面的结合和稳定。这种配方在缓冲溶液中（+4-37°C）具有良好的储存稳定性，在血清和玻璃体液中（+37°C）也具有足够的稳定性。ICG 在脂质双层内的结合和 PEG 涂层的组合导致在+22°C 和+37°C 的升高温度下稳定性差。通过分子动力学模拟阐明了由于 ICG 插入脂质双层而导致不稳定性增加的机制。在脂质双层中存在 ICG 的情况下，PEG 显著插入双层。最后，证明了冻干作为 ICG 脂质体长期储存方法的可行性。总的来说，这是首次详细研究脂质双层、光敏剂（ICG）和 PEG 涂层对脂质体稳定性的相互作用。光触发剂的定位显著改变了脂质体的结构，在设计触发药物递送系统时必须考虑这些方面。
