Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada.
Metrology Research Centre, National Research Council Canada, 100 Sussex Drive, Ottawa, ON, K1A 0R6, Canada.
Sci Rep. 2021 Feb 26;11(1):4768. doi: 10.1038/s41598-021-84131-x.
The development of reference standards for nanoparticle sizing allows for cross laboratory studies and effective transfer of particle sizing methodology. To facilitate this, these reference standards must be stable upon long-term storage. Here, we examine factors that influence the properties of cross-linked albumin nanoparticles, fabricated with an ethanol desolvation method, when reconstituted from a lyophilized state. We demonstrate, with nanoparticle tracking analysis, no significant changes in mean particle diameter upon reconstitution of albumin nanoparticles fabricated with bovine serum albumin loaded with dodecanoic acid, when compared to nanoparticles fabricated with a fatty acid-free BSA. We attribute this stability to the modulation of nanoparticle charge-charge interactions at dodecanoic acid specific binding locations. Furthermore, we demonstrate this in a lyophilized state over six months when stored at - 80 °C. We also show that the reconstitution process is readily transferable between technicians and laboratories and further confirm our finding with dynamic light scattering analysis.
纳米颗粒粒径参考标准的发展允许进行实验室间的研究和有效的颗粒粒径分析方法的转移。为此，这些参考标准必须在长期储存时保持稳定。在这里，我们研究了在从冻干状态重新配制时，用乙醇去溶剂化方法制备的交联白蛋白纳米颗粒的特性受到哪些因素的影响。我们通过纳米颗粒跟踪分析证明，与用不含脂肪酸的 BSA 制备的纳米颗粒相比，用负载有十二烷酸的牛血清白蛋白制备的白蛋白纳米颗粒在重新配制时，平均粒径没有明显变化。我们将这种稳定性归因于在十二烷酸特定结合位置调节纳米颗粒的电荷-电荷相互作用。此外，我们在-80°C 下储存六个月的冻干状态下证明了这一点。我们还表明，该重配过程在技术人员和实验室之间很容易转移，并进一步通过动态光散射分析确认了我们的发现。
