Effect of storage temperature on the stability of spray dried bacteriophage powders.
Effect of storage temperature on the stability of spray dried bacteriophage powders.
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DOI：
10.1016/j.ejpb.2018.02.033
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Chan HK
中科院分区：
文献类型：
--
作者：
Leung SSY;Parumasivam T;Nguyen A;Gengenbach T;Carter EA;Carrigy NB;Wang H;Vehring R;Finlay WH;Morales S;Britton WJ;Kutter E;Chan HK
本研究旨在评估使用喷雾干燥方法和配方设计生产可吸入噬菌体粉末的稳健性。研究了两种含有不同量海藻糖（70% 和 60%）和亮氨酸（30% 和 40%）的制剂中的两种类型的假单胞菌噬菌体：PEV2（足病毒）和 PEV40（肌病毒）。发现所生产的粉末的大部分表面被结晶亮氨酸覆盖。粉末在真空下储存于 4°C 和 20°C。在生产当天以及储存1、3和12个月后检查噬菌体粉末的噬菌体稳定性和体外气溶胶性能。两种噬菌体在生产过程中均观察到滴度轻微下降（0.2 – 0.8 log10 pfu/ml）。发现所生产的噬菌体粉末的储存稳定性取决于噬菌体和配方。在整个研究过程中，储存在 4°C 下的 PEV2 粉末滴度没有发生进一步降低。含有 30% 亮氨酸的制剂在 20 °C 下保持了 PEV2 的活力，而含有 40% 亮氨酸的制剂随着时间的推移逐渐失去效价，12 个月后测量，储存减少约 0.9 log10 pfu/ml。相比之下，无论温度如何，PEV40 噬菌体粉末在储存时通常有约 0.5 log10 pfu/ml 的损失。当雾化时，PEV2 的体外肺总剂量约为 107 pfu，但在 20°C 下储存的含有 40% 亮氨酸的制剂具有较低的肺剂量。 PEV40 粉末的肺部剂量也为 106 – 107 pfu。结果表明，喷雾干燥的肌病毒科和短足病毒科噬菌体在亮氨酸和海藻糖的简单配方中可以通过真空包装在 4 °C 和 20 °C 下成功保存一年。
This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine. The powders were stored at 4 °C and 20 °C under vacuum. The phage stability and in vitro aerosol performance of the phage powders were examined on the day of production and after 1, 3 and 12 months of storage. A minor titer loss during production was observed for both phages (0.2 – 0.8 log10 pfu/ml). The storage stability of the produced phage powders was found to be phage and formulation dependent. No further reduction in titer occurred for PEV2 powders stored at 4 °C across the study. The formulation containing 30% leucine maintained the viability of PEV2 at 20 °C, while the formulation containing 40% leucine gradually lost titer over time with a storage reduction of ~0.9 log10 pfu/ml measured after 12 months. In comparison, the PEV40 phage powders generally had a ~ 0.5 log10 pfu/ml loss upon storage regardless of temperature. When aerosolized, the total in vitro lung doses of PEV2 were of the order of 107 pfu, except the formulation containing 40% leucine stored at 20 °C which had a lower lung dose. The PEV40 powders also had lung doses of 106 – 107 pfu. The results demonstrate that spray dried Myoviridae and Podoviridae phage in a simple formulation of leucine and trehalose can be successfully stored for one year at 4 °C and 20 °C with vacuum packaging.
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