Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis.
Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis.
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DOI：
10.1016/j.nano.2015.02.012
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Shaunak S
中科院分区：
文献类型：
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作者：
Shirkhani K;Teo I;Armstrong-James D;Shaunak S
曲霉是移植患者中主要的危及生命的真菌病原体。吸入真菌孢子的萌发引起感染，引起严重的肺炎，死亡率为50%。这导致考虑暴露前预防，以防止感染。我们制备了一个非常低MWt的两性霉素b -聚甲基丙烯酸纳米颗粒。它对肺上皮细胞或单核细胞衍生的巨噬细胞在体外或在危及生命的侵袭性曲霉病的体内移植免疫抑制小鼠模型中没有毒性。三天的雾化器预防将纳米颗粒有效地输送到肺部，防止真菌生长和肺部炎症。对疾病的保护与曲霉杀死99%和肺TNF-α减少90%有关；组织破坏性免疫病理的主要驱动因素。这项研究提供了体内原理证明，非常小且成本效益高的纳米颗粒可以简单地制成，并通过气溶胶途径安全有效地输送到肺部，以预防真菌感染。曲霉是一种机会性病原体，影响免疫功能低下的患者。一种帮助对抗这种感染的新方法是暴露前预防。作者在此制备了以PMA为基础的阴离子水凝胶，携带两性霉素B，具有粘接行为。他们表明，在体内模型中，药物的气溶胶途径在预防疾病方面非常有效，并且应该为未来的临床试验提供踏脚石。雾化纳米颗粒预防侵袭性曲霉病。曲霉是移植患者中主要的危及生命的真菌病原体。它们会引起严重的肺炎，死亡率高达50%。因此，正在探索预防感染。这种极低MWt两性霉素b -聚甲基丙烯酸纳米颗粒作为气溶胶给予移植免疫抑制小鼠模型危及生命的侵袭性曲霉病。保护作用与曲霉的杀伤率达到99%，肺部TNF-α相关炎症减少90%有关。简单和具有成本效益的暴露前预防可预防侵袭性肺部真菌感染。
Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of > 50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with > 99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. Nebulised nanoparticle prevents invasive aspergillosis. Aspergillus species are the major life threatening fungal pathogens in transplant patients. They cause severe pneumonia with mortality of > 50%. Preventing infection is therefore being explored. This very low MWt amphotericin B-polymethacrylic acid nanoparticle was given as an aerosol to a transplant immuno-suppression mouse model with life threatening invasive aspergillosis. Protection was associated with > 99% killing of the Aspergillus and a 90% reduction in lung TNF-α related inflammation. Simple and cost-effective pre-exposure prophylaxis prevents invasive lung fungal infections.