吸入性穿心莲内酯-β-环糊精包合物通过调节免疫反应治疗<i>金黄色葡萄球菌性</i>肺炎,Molecular Pharmaceutics

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吸入性穿心莲内酯-β-环糊精包合物通过调节免疫反应治疗金黄色葡萄球菌性肺炎
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-04-05 00:00:00 , DOI: 10.1021/acs.molpharmaceut.6b01162
Tongtong Zhang _{1,

2} , Lifei Zhu _{1,

2} , Miao Li ₂ , Yuzhen Hu _{1,

2} , Erfeng Zhang ₃ , Qingcheng Jiang ₄ , Guang Han ₃ , Yiguang Jin _{1,

2,

3}

Affiliation

如果没有适当的立即治疗，细菌性肺炎是一种高死亡率的严重疾病。穿心莲内酯（AG）是从传统中草药穿心莲中提取的抗炎药。Oral AG片剂和药丸临床上用于治疗上呼吸道感染。然而，AG的低溶解度和生物利用度导致高剂量和长期治疗。在这里，我们开发了一种穿心莲内酯-β-环糊精包合物（AG-β-CD）用于金黄色葡萄球菌肺炎的吸入治疗。通过X射线衍射和FT-IR鉴定出AG-β-CD。令人惊讶的是，AG-β-CD和AG都没有表现出体外抗金黄色葡萄球菌的能力活动。然而，AG，AG-β-CD或青霉素的肺部递送具有明显的抗金黄色葡萄球菌。肺炎的影响。检测支气管肺泡灌洗液中的白细胞，中性粒细胞，白细胞，总蛋白，TNF-α，IL-6，NF-κBp65表达和细菌菌落。肺部递送AG和AG-β-CD通过调节免疫反应而导致细菌抑制和炎症减轻，而青霉素仅杀死细菌而没有明显的免疫调节。此外，AG-β-CD的抗肺炎活性远高于AG，这可能是由于β-CD包埋导致局部AG溶解加快所致。AG-β-CD粉末的空气动力学直径为2.03μm，适合肺部输送。可吸入的AG-β-CD是用于治疗金黄色葡萄球菌的有前途的抗菌和消炎药通过调节免疫反应来预防肺炎，β-CD包涵体可增强这种作用。由于其特定的作用机理，AG及其制剂可能是抵抗耐药细菌性肺炎的有效武器。

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Inhalable Andrographolide-β-cyclodextrin Inclusion Complexes for Treatment of Staphylococcus aureus Pneumonia by Regulating Immune Responses

Bacterial pneumonia is a serious disease with high mortality if no appropriate and immediate therapy is available. Andrographolide (AG) is an anti-inflammatory agent extracted from a traditional Chinese herb andrographis paniculata. Oral AG tablets and pills are clinically applied for treatment of upper respiratory tract infections. However, the low solubility and bioavailability of AG lead to high doses and long-term therapy. Here we developed an andrographolide-β-cyclodextrin inclusion complex (AG-β-CD) for inhalation therapy of Staphylococcus aureus pneumonia. AG-β-CD was identified with X-ray diffraction and FT-IR. Surprisingly, both AG-β-CD and AG showed little in vitro anti-S. aureus activity. However, pulmonary delivery of AG, AG-β-CD, or penicillin had significant anti-S. aureus pneumonia effects. Leukocytes, neutrophils, white blood cells, total proteins, TNF-α, IL-6, NF-κB p65 expression, and bacterial colonies in the bronchoalveolar lavage fluids were detected. Pulmonary delivery of AG and AG-β-CD led to bacterial inhibition and inflammation alleviation by regulating immune responses, while penicillin only killed bacteria without significant immune regulation. Moreover, the antipneumonia activity of AG-β-CD was much higher than that of AG, probably resulting from locally accelerated AG dissolution due to β-CD inclusion. The aerodynamic diameter of AG-β-CD powders was 2.03 μm, suitable for pulmonary delivery. Inhalable AG-β-CD is a promising antibacterial and anti-inflammatory medicine for the treatment of S. aureus pneumonia by regulating immune responses, and the effect is enhanced by β-CD inclusion. AG and its formulations might be potent weapons against the resistant bacterial pneumonia due to their specific mechanism in the future.

更新日期：2017-04-05

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