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研究封装工艺参数对电喷雾中治疗性病毒活力的影响。

Investigating the Effect of Encapsulation Processing Parameters on the Viability of Therapeutic Viruses in Electrospraying.

作者信息

Sanders Tayo, Milicic Anita, Stride Eleanor

机构信息

Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Old Road Campus Research Building, Headington OX3 7DQ, UK.

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Old Road Campus Research Building, Headington OX3 7DQ, UK.

出版信息

Pharmaceutics. 2020 Apr 24;12(4):388. doi: 10.3390/pharmaceutics12040388.

Abstract

The ability of viruses to introduce genetic material into cells can be usefully exploited in a variety of therapies and also vaccination. Encapsulating viruses to limit inactivation by the immune system before reaching the desired target and allowing for controlled release is a promising strategy of delivery. Conventional encapsulation methods, however, can significantly reduce infectivity. The aim of this study was to investigate electrospraying as an alternative encapsulation technique. Two commonly used therapeutic viruses, adenovirus (Ad) and modified vaccinia Ankara (MVA), were selected. First, solutions containing the viruses were electrosprayed in a single needle configuration at increasing voltages to examine the impact of the electric field. Second, the effect of exposing the viruses to pure organic solvents was investigated and compared to that occurring during coaxial electrospraying. Infectivity was determined by measuring the luminescence produced from lysed A549 cells after incubation with treated virus. Neither Ad nor MVA exhibited any significant loss in infectivity when electrosprayed within the range of electrospraying parameters relevant for encapsulation. A significant decrease in infectivity was only observed when MVA was electrosprayed at the highest voltage, 24 kV, and when MVA and Ad were exposed to selected pure organic solvents. Thus, it was concluded that electrospraying would be a viable method for virus encapsulation.

摘要

病毒将遗传物质导入细胞的能力在多种治疗方法以及疫苗接种中都能得到有效利用。在到达目标之前封装病毒以限制免疫系统的灭活作用并实现可控释放,是一种很有前景的递送策略。然而,传统的封装方法会显著降低病毒的感染性。本研究的目的是探究电喷雾作为一种替代封装技术的可行性。我们选择了两种常用的治疗性病毒,腺病毒(Ad)和改良安卡拉痘苗病毒(MVA)。首先,将含有病毒的溶液以单针配置在逐渐升高的电压下进行电喷雾,以研究电场的影响。其次,研究了病毒暴露于纯有机溶剂的效果,并与同轴电喷雾过程中发生的情况进行比较。通过测量与处理后的病毒孵育后裂解的A549细胞产生的发光来确定感染性。在与封装相关的电喷雾参数范围内进行电喷雾时,Ad和MVA的感染性均未表现出任何显著损失。仅在MVA以最高电压24 kV进行电喷雾时,以及MVA和Ad暴露于选定的纯有机溶剂时,才观察到感染性显著下降。因此,得出的结论是电喷雾将是一种可行的病毒封装方法。

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