Fumagalli Francesco, Welle Alexander, Bucher Guillaume, Appleton Silvia, Ponti Jessica, Ceccone Giacomo, Calzolai Luigi, Mehn Dora
European Commission, Joint Research Centre (JRC), Ispra, Italy.
Karlsruhe Nano Micro Facility (KNMF), Karlsruhe Institute of Technology (KIT), 76344, Eggenstein-Leopoldshafen, Germany.
Sci Rep. 2025 Jul 25;15(1):27060. doi: 10.1038/s41598-025-03947-z.
Liposomal drug delivery relies on polyethylene glycol (PEG) coating since it is essential for preserving the stability and increasing the plasma half-life of the lipid-based nanocarriers, and therefore it represents a critical quality attribute of nanomedicine formulations. Due to the complexity of their therapeutic action and the implications if they prove to be ineffective, decision-making in nanomedicine development requires statistically meaningful correlations between design principles and their biophysical properties. Precise characterization of PEG functional coatings is essential for quality control of PEGylated liposomes, it is required not only to measure the total amount of nanoparticle incorporated PEG-chains but also their abundance and conformation at the nanoparticle external surface. In this study, we developed a methodology to characterize PEG-coatings of PEGylated liposomes using a cryogenic protocol for time-of-flight secondary ions mass spectrometry (ToF-SIMS). The method was applied to liposomes formulated with varying PEG-lipid contents in the formulation and the measurements successfully distinguished PEGylated liposomes based on their PEG-lipid content in the liposome outer membranes. These results indicate that the cryogenic ToF-SIMS method could be potentially used to control the quality of PEGylated liposomes not only for research and but also for drug manufacturing processes.
脂质体药物递送依赖于聚乙二醇（PEG）包衣，因为这对于保持基于脂质的纳米载体的稳定性和延长其血浆半衰期至关重要，因此它是纳米药物制剂的一个关键质量属性。由于其治疗作用的复杂性以及如果证明无效所带来的影响，纳米药物开发中的决策需要设计原则与其生物物理性质之间具有统计学意义的相关性。PEG功能涂层的精确表征对于聚乙二醇化脂质体的质量控制至关重要，不仅需要测量纳米颗粒结合的PEG链的总量，还需要测量其在纳米颗粒外表面的丰度和构象。在本研究中，我们开发了一种方法，使用低温飞行时间二次离子质谱（ToF-SIMS）对聚乙二醇化脂质体的PEG涂层进行表征。该方法应用于配方中PEG-脂质含量不同的脂质体，测量结果成功地根据脂质体外膜中的PEG-脂质含量区分了聚乙二醇化脂质体。这些结果表明，低温ToF-SIMS方法不仅可用于研究，还可用于药物制造过程中聚乙二醇化脂质体的质量控制。
