Effects of storage conditions on the stability of spray dried, inhalable bacteriophage powders.
Effects of storage conditions on the stability of spray dried, inhalable bacteriophage powders.
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DOI：
10.1016/j.ijpharm.2017.01.060
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发表时间：
2017-04-15
影响因子：
5.8
通讯作者：
Chan HK
中科院分区：
文献类型：
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作者：
Leung SSY;Parumasivam T;Gao FG;Carter EA;Carrigy NB;Vehring R;Finlay WH;Morales S;Britton WJ;Kutter E;Chan HK
本研究旨在开发用于肺部给药的含抗耐药铜绿假单胞菌活性物质的可吸入粉末。将假单胞菌噬菌体PEV 2喷雾干燥成包含海藻糖（0-80%）、甘露醇（0-80%）和L-亮氨酸（20%）的粉末基质。将所得粉末在4 °C下储存在各种相对湿度（RH）条件（0、22和60%RH）下。在生产时和储存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。喷雾干燥后，在含有40%、60%和80%海藻糖的制剂中观察到噬菌体滴度总共减少1.3个对数，而在含有20%和不含海藻糖的制剂中分别观察到2.4和5.1个对数减少。除不含海藻糖的制剂外，即使在0和22%RH下储存12个月后，粉末的滴度也未进一步降低。60% RH储存条件具有破坏性影响，因此在3个月和12个月后未检测到活菌。当雾化时，含40%、60%和80%海藻糖的制剂的总肺剂量相似（约为105 pfu）。结果表明，喷雾干燥是生产用于肺部递送的稳定噬菌体粉末的合适方法。含≥ 40%海藻糖的粉末基质在0和22%RH、4 °C下储存12个月后提供了良好的噬菌体保存和气雾剂性能。在0%、22%和60% RH下储存后F1 - F4制剂中的噬菌体稳定性。0个月（新鲜）、1个月、3个月和12个月时的滴度降低相对于喷雾干燥器液体原料中测得的滴度。
This study aimed to develop inhalable powders containing phages active against antibiotic-resistant Pseudomonas aeruginosa for pulmonary delivery. A Pseudomonas phage, PEV2, was spray dried into powder matrices comprising of trehalose (0–80%), mannitol (0–80%) and L-leucine (20%). The resulting powders were stored at various relative humidity (RH) conditions (0, 22 and 60% RH) at 4 °C. The phage stability and in vitro aerosol performance of the phage powders were examined at the time of production and after 1, 3 and 12 months storage. After spray drying, a total of 1.3 log titer reduction in phage was observed in the formulations containing 40%, 60% and 80% trehalose, whereas 2.4 and 5.1 log reductions were noted in the formulations containing 20% and no trehalose, respectively. No further reduction in titer occurred for powders stored at 0 and 22% RH even after 12 months, except the formulation containing no trehalose. The 60% RH storage condition had a destructive effect such that no viable phages were detected after 3 and 12 months. When aerosolised, the total lung doses for formulations containing 40%, 60% and 80% trehalose were similar (in the order of 105 pfu). The results demonstrated that spray drying is a suitable method to produce stable phage powders for pulmonary delivery. A powder matrix containing ≥ 40% trehalose provided good phage preservation and aerosol performances after storage at 0 and 22 % RH at 4 °C for 12 months. Phage Stability in F1 – F4 formulation after storage at 0%, 22% and 60% RH. Titer reductions at 0 months (Fresh), 1, 3 and 12 months are relative to the titer measured in the spray dryer liquid feedstock.