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大气道炎症和 5nm 聚乙二醇化及柠檬酸金纳米颗粒在哮喘小鼠系统摄取的局部效应

Local Effects on Airway Inflammation and Systemic Uptake of 5 nm PEGylated and Citrated Gold Nanoparticles in Asthmatic Mice.

机构信息

Department of Experimental Pneumology and Allergology, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.

Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.

出版信息

Small. 2017 Mar;13(10). doi: 10.1002/smll.201603070. Epub 2016 Dec 23.

DOI:10.1002/smll.201603070
PMID:28009478
Abstract

Nanotechnology is showing promise in many medical applications such as drug delivery and hyperthermia. Nanoparticles administered to the respiratory tract cause local reactions and cross the blood-air barrier, thereby providing a means for easy systemic administration but also a potential source of toxicity. Little is known about how these effects are influenced by preexisting airway diseases such as asthma. Here, BALB/c mice are treated according to the ovalbumin (OVA) asthma protocol to promote allergic airway inflammation. Dispersions of polyethylene-glycol-coated (PEGylated) and citrate/tannic-acid-coated (citrated) 5 nm gold nanoparticles are applied intranasally to asthma and control groups, and (i) airway resistance and (ii) local tissue effects are measured as primary endpoints. Further, nanoparticle uptake into extrapulmonary organs is quantified by inductively coupled plasma mass spectrometry. The asthmatic precondition increases nanoparticle uptake. Moreover, systemic uptake is higher for PEGylated gold nanoparticles compared to citrated nanoparticles. Nanoparticles inhibit both inflammatory infiltrates and airway hyperreactivity, especially citrated gold nanoparticles. Although the antiinflammatory effects of gold nanoparticles might be of therapeutic benefit, systemic uptake and consequent adverse effects must be considered when designing and testing nanoparticle-based asthma therapies.

摘要

纳米技术在许多医学应用中显示出了应用前景,如药物输送和热疗。递送至呼吸道的纳米颗粒会引起局部反应并穿过血-气屏障,从而为简便的全身给药提供了一种途径,但也可能成为毒性的潜在来源。目前尚不清楚这些影响如何受哮喘等先前存在的气道疾病的影响。在这里,根据卵清蛋白 (OVA) 哮喘方案对 BALB/c 小鼠进行治疗,以促进过敏性气道炎症。聚乙二醇 (PEG) 涂层和柠檬酸/单宁酸 (citrated) 涂层的 5nm 金纳米颗粒分散体被鼻内应用于哮喘和对照组,并测量 (i) 气道阻力和 (ii) 局部组织效应作为主要终点。此外,通过电感耦合等离子体质谱法定量测定纳米颗粒进入肺外器官的摄取量。哮喘预处理增加了纳米颗粒的摄取。此外,与 citrated 纳米颗粒相比,PEG 化金纳米颗粒的全身摄取量更高。纳米颗粒抑制炎症浸润和气道高反应性,特别是 citrated 金纳米颗粒。尽管金纳米颗粒的抗炎作用可能具有治疗益处,但在设计和测试基于纳米颗粒的哮喘疗法时,必须考虑全身摄取和随之而来的不良反应。

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