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基于纳米的慢性阻塞性肺疾病治疗学:挑战与治疗潜力。

Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential.

出版信息

Expert Opin Drug Deliv. 2011 Sep;8(9):1105-9. doi: 10.1517/17425247.2011.597381. Epub 2011 Jun 28.

Abstract

The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke. Controlling chronic inflammation is at the root of treatments such as corticosteroids, antibiotics or other available drugs, which pose the challenge of sustained delivery of drugs to target cells or tissues. In spite of the wide application of nano-based drug delivery systems, very few are tested to date. Targeted nanoparticle-mediated sustained drug delivery is required to control inflammatory cell chemotaxis, fibrosis, protease-mediated chronic emphysema and/or chronic lung obstruction in COPD. Moreover, targeted epithelial delivery is indispensable for correcting the underlying defects in CF and targeted inflammatory cell delivery for controlling other chronic inflammatory lung diseases. We propose that the design and development of nano-based targeted theranostic vehicles with therapeutic, imaging and airway-defense penetrating capability, will be invaluable for treating chronic obstructive lung diseases. This paper discusses a novel nano-theranostic strategy that we are currently evaluating to treat the underlying cause of CF and COPD lung disease.

摘要

在慢性阻塞性气道疾病中,纳米递药系统的输送和治疗效果面临的主要挑战是气道防御、严重炎症和黏液高分泌。慢性气道炎症和黏液高分泌是包括哮喘、COPD(慢性阻塞性肺疾病)和 CF(囊性纤维化)在内的慢性阻塞性气道疾病的特征。这些疾病的炎症和黏液高分泌是由不同的病因引起的,进一步由感染或香烟烟雾的成分引发。控制慢性炎症是皮质类固醇、抗生素或其他现有药物治疗的根本,这些药物存在将药物持续递送到靶细胞或组织的挑战。尽管纳米药物递送系统得到了广泛应用,但迄今为止只有很少的系统得到了测试。需要靶向纳米颗粒介导的持续药物输送来控制 COPD 中的炎症细胞趋化、纤维化、蛋白酶介导的慢性肺气肿和/或慢性肺阻塞。此外,上皮细胞的靶向递药对于纠正 CF 的根本缺陷,以及靶向炎症细胞递药对于控制其他慢性炎症性肺病是不可或缺的。我们提出,具有治疗、成像和气道防御穿透能力的基于纳米的靶向治疗诊断载体的设计和开发,对于治疗慢性阻塞性肺病将是非常宝贵的。本文讨论了我们目前正在评估的一种新型纳米治疗策略,用于治疗 CF 和 COPD 肺病的根本原因。

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