Spray dried tigecycline dry powder aerosols for the treatment of Nontuberculous mycobacterial pulmonary infections.
Spray dried tigecycline dry powder aerosols for the treatment of Nontuberculous mycobacterial pulmonary infections.
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喷雾干燥的tigecycline干粉气管可用于治疗非结核分枝杆菌肺部感染。
DOI：
10.1016/j.tube.2023.102306
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发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Hickey AJ
中科院分区：
文献类型：
--
作者：
Maloney SE;Alshiraihi IM;Singh A;Stewart IE;Mariner Gonzalez J;Gonzalez-Juarrero M;Meibohm B;Hickey AJ
非结核分枝杆菌（NTM）肺部感染是一个全球性的健康问题，是肺部疾病的重要因素。长期给予抗生素鸡尾酒的全身治疗通常会导致不良反应和/或治疗失败。众所周知，NTM病原体，如分枝杆菌（Mabs），由于对许多传统抗生素的耐药性而难以治疗。然而，抗生素替加环素已在体外和体内对药物敏感性不同的Mab菌株显示出有效性。替加环素在水性介质中表现出不稳定性，造成递送挑战，并且在静脉内给药后引起严重的不良胃肠道反应，需要停止治疗。为了缓解这两个问题，使用干粉气雾剂的吸入疗法被提议作为替代给药途径和递送方式。制备、表征和优化替加环素干粉制剂，以开发具有低水分、高膨胀率和大部分可吸入粒径范围（1-5 μm）的颗粒的治疗气雾剂。研究了乳糖、亮氨酸和磷酸盐缓冲盐的添加以实现额外的稳定性、耐受性和耐受性。初步交付的干粉Mabs感染的小鼠30分钟，每天超过7天证明了0.91对数（87.7%）减少肺部细菌负荷。
Nontuberculous mycobacterial (NTM) pulmonary infections are a global health concern and a significant contributor to lung disease. Systemic therapies of a cocktail of antibiotics administered over a long period often lead to adverse reactions and/or treatment failure. NTM pathogens, such as Mycobacterium abscessus (Mabs), are notoriously difficult to treat due to resistance to many traditional antibiotics. However, the antibiotic tigecycline has demonstrated efficacy in vitro and in vivo against Mabs strains varying in drug susceptibility. Tigecycline exhibits instability in aqueous medium, posing delivery challenges, and has caused severe adverse gastrointestinal effects following intravenous administration, requiring treatment discontinuation. To mitigate both of these concerns, inhalation therapies using dry powder aerosols are proposed as an alternative administration route and means of delivery. Tigecycline dry powder formulations were prepared, characterized, and optimized to develop a therapeutic aerosol with low moisture, high dispersibility, and a large fraction of particles in the respirable size range (1–5 μm). The addition of lactose, leucine, and phosphate buffer salts was investigated to achieve additional stability, dispersibility, and tolerability. Preliminary delivery of the dry powders to Mabs-infected mice for 30 min per day over 7 d demonstrated a 0.91-log (87.7%) decrease in lung bacterial burden.
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