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用于阻塞性肺病药物递送的气道靶向聚乳酸-羟基乙酸共聚物-聚乙二醇纳米颗粒的合成与评价

Synthesis and Evaluation of Airway-Targeted PLGA-PEG Nanoparticles for Drug Delivery in Obstructive Lung Diseases.

作者信息

Vij Neeraj

机构信息

Department of Pediatrics and Pulmonary Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

4Dx Limited, Los Angeles, CA, USA.

出版信息

Methods Mol Biol. 2020;2118:147-154. doi: 10.1007/978-1-0716-0319-2_11.

Abstract

Chronic airway inflammation is a hallmark of chronic obstructive airway diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma. Airway inflammation and mucus obstruction present major challenges to drug or gene delivery and therapeutic efficacy of nano-based carriers in these chronic obstructive airway conditions. To achieve targeted drug delivery of NPs to the diseased cells, NPs need to bypass the obstructive airway and circumvent the airway's defense mechanisms. Although there has been increasing interest and significant progress in development of NPs for targeting cancer, relatively little progress has been made towards designing novel systems for targeted treatment of chronic inflammatory and obstructive airway conditions. Hence, we describe here methods for preparing drug loaded multifunctional nanoparticles for targeted delivery to specific airway cell types in obstructive lung diseases. The formulations and methods for selective drug delivery in the treatment of chronic airway conditions such as COPD, CF, and asthma have been evaluated using a variety of preclinical models by our laboratory and currently ongoing further clinical development for translation from bench to bedside.

摘要

慢性气道炎症是慢性阻塞性气道疾病的一个标志,这些疾病包括慢性阻塞性肺疾病(COPD)、囊性纤维化(CF)和哮喘。气道炎症和黏液阻塞对纳米载体在这些慢性阻塞性气道疾病中的药物或基因递送以及治疗效果构成了重大挑战。为了实现纳米颗粒向患病细胞的靶向药物递送,纳米颗粒需要绕过阻塞性气道并规避气道的防御机制。尽管在开发用于靶向癌症的纳米颗粒方面兴趣日益浓厚且取得了显著进展,但在设计用于靶向治疗慢性炎症性和阻塞性气道疾病的新型系统方面进展相对较小。因此,我们在此描述了制备负载药物的多功能纳米颗粒以靶向递送至阻塞性肺病中特定气道细胞类型的方法。我们实验室已使用多种临床前模型评估了在治疗慢性气道疾病如COPD、CF和哮喘中进行选择性药物递送的制剂和方法,目前正在进行进一步的临床开发以便从实验室转化到临床应用。

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