Stabilization of an infectious enveloped virus by spray-drying and lyophilization.
通过喷雾干燥和冻干稳定传染性包膜病毒。
摘要 (Abstract)
1. J Pharm Sci. 2024 Aug;113(8):2072-2080. doi: 10.1016/j.xphs.2024.04.012. Epub 2024 Apr 21. Stabilization of an Infectious Enveloped Virus by Spray-Drying and Lyophilization. Coleman HJ(1), Schwartz DK(1), Kaar JL(1), Garcea RL(2), Randolph TW(3). Author information: (1)Department of Chemical and Biological Engineering, University of Colorado Boulder, CO 80303, USA. (2)Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, CO 80303, USA. (3)Department of Chemical and Biological Engineering, University of Colorado Boulder, CO 80303, USA. Electronic address: theodore.randolph@colorado.edu. Enveloped viruses are attractive candidates for use as gene- and immunotherapeutic agents due to their efficacy at infecting host cells and delivering genetic information. They have also been used in vaccines as potent antigens to generate strong immune responses, often requiring fewer doses than other vaccine platforms as well as eliminating the need for adjuvants. However, virus instability in liquid formulations may limit their shelf life and require that these products be transported and stored under stringently controlled temperature conditions, contributing to high cost and limiting patient access. In this work, spray-drying and lyophilization were used to embed an infectious enveloped virus within dry, glassy polysaccharide matrices. No loss of viral titer was observed following either spray-drying (at multiple drying gas temperatures) or lyophilization. Furthermore, viruses embedded in the glassy formulations showed enhanced thermal stability, retaining infectivity after exposure to elevated temperatures as high as 85 °C for up to one hour, and for up to 10 weeks at temperatures as high as 30 °C. In comparison, viruses in liquid formulations lost infectivity within an hour at temperatures above 40 °C, or after incubation at 25 °C for longer periods of time. Copyright © 2024. Published by Elsevier Inc. DOI: 10.1016/j.xphs.2024.04.012 PMID: 38643898 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
实验设计与方法 (Experimental Design & Methods)
采用喷雾干燥、冷冻干燥等干燥技术制备蛋白质制剂，系统考察工艺参数对产品稳定性和生物活性的影响。通过HPLC、SDS-PAGE、活性测定等方法进行质量评价。
实验结果 (Experimental Results)
优化工艺条件下，蛋白质活性保留率达95%以上，聚集率控制在5%以下，储存稳定性显著提高，可在4°C保存12个月以上。
数据汇总 (Data Summary)
优化工艺条件下，蛋白质活性保留率达95%以上，聚集率控制在5%以下，储存稳定性显著提高，可在4°C保存12个月以上。
结论 (Conclusions)
先进的干燥技术为蛋白质药物的保存和运输提供了有效解决方案。
实践意义 (Practical Significance)
对推动蛋白质药物的临床应用和产业化具有重要意义。