Shirkhani Khojasteh, Teo Ian, Armstrong-James Darius, Shaunak Sunil
Departments of Medicine, Infectious Diseases, Immunity and Chemistry, Imperial College London, Hammersmith campus, London, UK.
Departments of Medicine, Infectious Diseases, Immunity and Chemistry, Imperial College London, Hammersmith campus, London, UK.
Nanomedicine. 2015 Jul;11(5):1217-26. doi: 10.1016/j.nano.2015.02.012. Epub 2015 Mar 16.
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.
曲霉属是移植患者中主要的危及生命的真菌病原体。吸入的真菌孢子萌发引发感染，导致严重肺炎，死亡率超过50%。这促使人们考虑进行暴露前预防以防止感染。我们制备了一种极低分子量的两性霉素B - 聚甲基丙烯酸纳米颗粒。它在体外对肺上皮细胞或单核细胞衍生的巨噬细胞无毒，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也无毒。基于雾化器的三天预防可将纳米颗粒有效地递送至肺部，并预防真菌生长和肺部炎症。对疾病的保护与>99%的曲霉杀灭率以及肺部肿瘤坏死因子 - α降低90%相关；肿瘤坏死因子 - α是组织破坏性免疫病理学的主要驱动因素。这项研究提供了体内原理证明，即可以简单地制备非常小且经济高效的纳米颗粒，并通过气溶胶途径安全有效地递送至肺部以预防真菌感染。
曲霉是一种机会性病原体，会影响免疫功能低下的患者。一种对抗这种感染的新方法是暴露前预防。作者在此制备了携带两性霉素B的基于聚甲基丙烯酸的阴离子水凝胶，具有粘膜粘附行为。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，应为未来的临床试验提供一个跳板。
