药学学报, 2016, 51(12): 1906-1912
引用本文:
胡玉贞, 李淼, 张桐桐, 金义光. 青蒿琥酯脂质体粉雾剂的制备及其治疗大鼠急性肺损伤的作用[J]. 药学学报, 2016, 51(12): 1906-1912.
HU Yu-zhen, LI Miao, ZHANG Tong-tong, JIN Yi-guang. Preparation of liposomal artesunate dry powder inhalers and the effect on the acute lung injury of rats[J]. Acta Pharmaceutica Sinica, 2016, 51(12): 1906-1912.

青蒿琥酯脂质体粉雾剂的制备及其治疗大鼠急性肺损伤的作用
胡玉贞1, 李淼2, 张桐桐1, 金义光1,2
1. 安徽医科大学, 安徽 合肥 230032;
2. 军事医学科学院放射与辐射医学研究所, 北京 100850
摘要:
青蒿琥酯是青蒿素衍生物,具有抗炎和抗疟疾作用,但其难溶于水,口服吸收差。急性肺损伤(acute lung injury,ALI)是一种严重的弥漫性肺部疾病,具有进程快和死亡率高的特点。本文用薄膜分散法制备了青蒿琥酯脂质体,冻干后得到粉雾剂(dry powder inhalers,DPI),经肺吸入后用于治疗ALI。青蒿琥酯脂质体的包封率为71.4%,粒径为47.3 nm,zeta电位为-13.7 mV。粉雾剂的空气动力学粒径为4.2 μm,体外肺部沉积率为34.5%。将脂多糖(lipopolysaccharide,LPS)经气管喷入大鼠肺中成功建立ALI大鼠模型。大鼠很快出现自主活动明显减少、精神萎靡、呼吸加快和腹泻等症状。1 h后,将青蒿琥酯脂质体粉雾剂(liposomal artesunate dry powder inhalers,LADPIs)经气管直接喷入ALI大鼠肺内。LADPIs治疗组与模型组比较,症状减轻。DPI组的炎症因子TNF-α和IL-6水平低于青蒿琥酯原料药组和阳性药地塞米松组(P<0.05),表明青蒿琥酯治疗ALI的主要机制为抗炎作用,并且脂质体粉雾剂剂型可增加药物肺内利用,提高疗效。LADPIs有望成为治疗ALI的有效制剂。
关键词:   
Preparation of liposomal artesunate dry powder inhalers and the effect on the acute lung injury of rats
HU Yu-zhen1, LI Miao2, ZHANG Tong-tong1, JIN Yi-guang1,2
1. Anhui Medicine University, Hefei 230032, China;
2. Institute of Radiation Medicine, Academy of Military Medical Sciences, Bejing 100850, China
Abstract:
Artesunate is one of artemisinin derivatives with anti-malarial and anti-inflammatory activities though its water solubility and bioavailability are low. Acute lung injury (ALI) is a seriously dispersive lung disease with a high mortality. In this study, artesunate liposomes were prepared with the film dispersion method, and then lyophilized to obtain the liposomal artesunate dry powder inhalers (LADPIs). The LADPIs were pulmonary-delivered into the lung to treat ALI in rats. The artesunate liposomes had the capsulation efficiency of 71.4%, the particle size of 47.3 nm, and the zeta potential of -13.7 mV. The LADPIs had the aerodynamic particle size of 4.2 μm and the fine particle fraction (FPF) of 34.5%. ALI was established in rats by instilling lipopolysaccharide (LPS) into the lungs. The rats quickly showed a reduction in movement and acceleration in breath followed by diarrhea and so on. The LADPIs were directly administrated into the lungs of ALI rats through airways after 1 h of LPS challenge. The treatment induced a reduction in ALI syndromes. Two inflammatory factors, including TNF-α and IL-6, were significantly reduced by the artesunate powder in the LADPI group similarly to the reduction in the positive drug dexamethasone group (P<0.05). Therefore, the anti-inflammatory effect of LADPIs contributed to the anti-ALI activity. Furthermore, the liposomal formulation improved drug bioavailability in the lung and increased therapeutic efficiency. The LADPIs are promising medicines for therapy of ALI through local drug administration.
Key words:   
收稿日期: 2016-08-29
DOI: 10.16438/j.0513-4870.2016-0848
基金项目: 国家科技重大专项资助项目(2012ZX09301003-001-009);北京市自然科学基金青年项目资助(7154230).
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