Spray-Dried Respirable Powders Containing Bacteriophages for the Treatment of Pulmonary Infections
Spray-Dried Respirable Powders Containing Bacteriophages for the Treatment of Pulmonary Infections
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DOI：
10.1002/jps.22715
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发表时间：
2011-12-01
影响因子：
3.8
通讯作者：
Vehring, Reinhard
中科院分区：
文献类型：
--
作者：
Matinkhoo, Sadaf;Lynch, Karlene H.;Vehring, Reinhard
利用低温喷雾干燥工艺将Myoviridae噬菌体加工成干粉可吸入剂型。噬菌体被掺入由海藻糖、亮氨酸和可选的第三种赋形剂(表面活性剂或酪蛋白钠盐)组成的微粒中。这些颗粒被设计成具有高分散性和可呼吸的颗粒大小，并在加工过程中保存噬菌体。噬菌体KS4-M、KS14以及噬菌体Phi KZ/D3和Phi KZ/D3/KS4-M的鸡尾酒被喷雾干燥，加工损失在0.4-0.8logPFU之间。由Aerolizer(R)干粉吸入器(DPI)提供的干粉的气雾剂性能超过了商用DPI的性能；铅制剂的排放质量和体外总肺质量分别为填充胶囊质量的82.7%和69.7%。肺总质量的空气动力学质量中值直径为2.5-2.8微米。单次驱动吸入器释放的噬菌体体外总肺剂量为107-108pfu，在体内有望达到有效水平。将噬菌体喷雾干燥成可呼吸的干粉是可行的。(C)2011年Wiley-Liss，Inc.和美国药剂师协会《医药科学》100：5197-5205,2011
Myoviridae bacteriophages were processed into a dry powder inhalable dosage form using a low-temperature spray-drying process. The phages were incorporated into microparticles consisting of trehalose, leucine, and optionally a third excipient (either a surfactant or casein sodium salt). The particles were designed to have high dispersibility and a respirable particle size, and to preserve the phages during processing. Bacteriophages KS4- M, KS14, and cocktails of phages Phi KZ/D3 and Phi KZ/D3/KS4-M were spray-dried with a processing loss ranging from 0.4 to 0.8 log pfu. The aerosol performance of the resulting dry powders as delivered from an Aerolizer (R) dry powder inhaler (DPI) exceeded the performance of commercially available DPIs; the emitted mass and the in vitro total lung mass of the lead formulation were 82.7% and 69.7% of filled capsule mass, respectively. The total lung mass had a mass median aerodynamic diameter of 2.5-2.8 mu m. The total in vitro lung doses of the phages, delivered from a single actuation of the inhaler, ranged from 107 to 108 pfu, levels that are expected to be efficacious in vivo. Spray drying of bacteriophages into a respirable dry powder was found to be feasible. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:5197-5205, 2011