Khramtsov Pavel, Burdina Oksana, Lazarev Sergey, Novokshonova Anastasia, Bochkova Maria, Timganova Valeria, Kiselkov Dmitriy, Minin Artem, Zamorina Svetlana, Rayev Mikhail
Perm Federal Research Center of the Ural Branch of The Russian Academy of Sciences, Lab of Ecological Immunology, Institute of Ecology and Genetics of Microorganisms, 614081 Perm, Russia.
Department of Biology, Perm State University, 614068 Perm, Russia.
Pharmaceutics. 2021 Sep 22;13(10):1537. doi: 10.3390/pharmaceutics13101537.
Gelatin nanoparticles found numerous applications in drug delivery, bioimaging, immunotherapy, and vaccine development as well as in biotechnology and food science. Synthesis of gelatin nanoparticles is usually made by a two-step desolvation method, which, despite providing stable and homogeneous nanoparticles, has many limitations, namely complex procedure, low yields, and poor reproducibility of the first desolvation step. Herein, we present a modified one-step desolvation method, which enables the quick, simple, and reproducible synthesis of gelatin nanoparticles. Using the proposed method one can prepare gelatin nanoparticles from any type of gelatin with any bloom number, even with the lowest ones, which remains unattainable for the traditional two-step technique. The method relies on quick one-time addition of poor solvent (preferably isopropyl alcohol) to gelatin solution in the absence of stirring. We applied the modified desolvation method to synthesize nanoparticles from porcine, bovine, and fish gelatin with bloom values from 62 to 225 on the hundreds-of-milligram scale. Synthesized nanoparticles had average diameters between 130 and 190 nm and narrow size distribution. Yields of synthesis were 62-82% and can be further increased. Gelatin nanoparticles have good colloidal stability and withstand autoclaving. Moreover, they were non-toxic to human immune cells.
明胶纳米颗粒在药物递送、生物成像、免疫治疗、疫苗开发以及生物技术和食品科学等领域有广泛应用。明胶纳米颗粒的合成通常采用两步去溶剂化法,尽管该方法能提供稳定且均匀的纳米颗粒,但存在诸多局限性,如步骤复杂、产率低以及第一步去溶剂化步骤的重现性差。在此,我们提出一种改进的一步去溶剂化法,该方法能够快速、简单且可重复地合成明胶纳米颗粒。使用所提出的方法,可以从任何类型、任何勃氏硬度值的明胶制备明胶纳米颗粒,即使是最低勃氏硬度值的明胶,这是传统两步法无法实现的。该方法依赖于在不搅拌的情况下,将不良溶剂(优选异丙醇)快速一次性加入到明胶溶液中。我们应用改进的去溶剂化法,以数百毫克规模从猪、牛和鱼明胶合成纳米颗粒,勃氏硬度值在62至225之间。合成的纳米颗粒平均直径在130至190纳米之间,粒径分布窄。合成产率为62 - 82%,且可进一步提高。明胶纳米颗粒具有良好的胶体稳定性,能耐受高压灭菌。此外,它们对人类免疫细胞无毒。