Liposomal andrographolide dry powder inhalers for treatment of bacterial pneumonia via anti-inflammatory pathway
Liposomal andrographolide dry powder inhalers for treatment of bacterial pneumonia via anti-inflammatory pathway
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DOI：
10.1016/j.ijpharm.2017.06.005
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发表时间：
2017-08-07
影响因子：
5.8
通讯作者：
Jin, Yiguang
中科院分区：
文献类型：
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作者：
Li, Miao;Zhang, Tongtong;Jin, Yiguang
穿心莲（AG）是一种传统中药化学实体，其口服丸剂已被用于治疗呼吸道炎症。在这里，我们报告肺部交付的脂质体AG干粉吸入器（LADPI）治疗金黄色葡萄球菌引起的肺炎。采用注射法制备AG脂质体，冷冻干燥制备LADPI。AG脂质体小而稳定，平均粒径为77.91 nm，zeta电位为-56.13 mV。脂质体在LADPI再水化后恢复良好，其适于肺部递送，质量平均空气动力学直径（MMAD）为4.87 μ m，细颗粒分数（FPF）为23.03%。然而，AG粉末的MMAD和FPF分别为10.14 μ m和8.37%。体外抗S.将AG粉和LADPI分别喷雾于大鼠肺内治疗金黄色葡萄球菌，观察其对金黄色葡萄球菌的作用。金黄色肺炎令人惊讶的是，LADPI显示出更强的抗S。金黄色葡萄球菌肺炎在体内的作用，比AG在十倍的剂量或比抗生素，青霉素。LADPI显著降低了许多促炎细胞因子，包括TNF-α、IL-1。此外，核因子-κ B（NF-κ B）通路中IkB-α的磷酸化也被显著抑制。AG通过调节免疫反应维持抗菌作用，同时下调炎症反应，对细菌性肺炎有较强的治疗作用。LADPI是一种有前途的肺部给药药物，用于治疗细菌性肺炎。(C)2017爱思唯尔B. V.保留所有权利。
Andrographolide (AG) is a chemical entity from traditional Chinese herbs and its oral pills have been applied to the treatment of respiratory inflammation. Here we report pulmonary delivery of liposomal AG dry powder inhalers (LADPIs) for treatment of Staphylococcus aureus-induced pneumonia. AG liposomes were prepared with the injection method and then freeze-dried for preparation of LADPIs. AG liposomes were small and stable with a mean size of 77.91 nm and a zeta potential of -56.13 mV. Liposomes were well recovered after re-hydration of LADPIs that were suitable for pulmonary delivery with a mass mean aerodynamic diameter (MMAD) of 4.87 mu m and a fine particle fraction (FPF) of 23.03%. However, the MMAD and FPF of AG powders were 10.14 mu m and 8.37%, respectively. The in vitro anti-S. aureus effects of AG powders and LADPIs were investigated, but were not found. They were intratracheally sprayed into the rat lungs for treatment of S. aureus pneumonia. Surprisingly, LADPIs showed a stronger anti-S. aureus pneumonic effect in vivo, than AG at a ten-fold dose or than an antibiotic, penicillin. LADPIs significantly decreased many pro-inflammatory cytokines including TNF-alpha, IL-1. Furthermore, the phosphorylation of IkB-alpha in the nuclear factor-kappa B (NF-kappa B) pathway was also remarkably inhibited. AG regulated the immune reaction to maintain the antibacterial effect while downregulating inflammatory response so that AG showed a strong effect on bacterial pneumonia. LADPIs are a promising pulmonary delivery medicine for the treatment of bacterial pneumonia. (C) 2017 Elsevier B.V. All rights reserved.