An advanced inhalable dry powder, mucus-penetrating aerosol platform: Bridging Andrographolide delivery with clinical translation

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-05-08 DOI:10.1016/j.biomaterials.2025.123401

Decui Cheng , Tingting Pan , Xiaoli Wang , Rui Tian , Huizhen Fan , Li Wei , Shiyuan He , Ruonan Dong , Xiangqun Yan , Mei X. Wu , Ruoming Tan , Hongping Qu , Min Lu

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引用次数: 0

Abstract

Effective aerosol drug delivery remains a challenge for treating pulmonary diseases due to physiological barriers such as mucus accumulation, biofilm formation, and rapid macrophage clearance. Here, we developed an inhalable honeycomb-like microsphere (HCLplga-Ab) aerosol platform using FDA-approved poly(lactic-co-glycolic acid) (PLGA) and a pore-forming agent. The platform encapsulates Andrographolide, a bioactive compound derived from traditional Chinese medicine, together with a chitosan-ambroxol coating to achieve mucus penetration, sequential drug release, and prolonged retention in the lungs. The large geometric diameter (∼10–15 μm) combined with an optimal aerodynamic size (∼2.57 μm) ensures deep lung deposition while evading alveolar macrophage clearance. In murine models of acute lung injury (ALI), bacterial pneumonia (Klebsiella pneumoniae), and fungal pneumonia (Candida albicans), HCLplga-Ab demonstrated enhanced mucus penetration and biofilm destruction, uniform and prolonged drug retention in the lungs, and significant reduction in inflammation and pathogen burden. This versatile platform bridges traditional medicine with modern aerosol technology, offering a promising solution for respiratory disorders and clinical translation.

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一个先进的可吸入干粉，粘液穿透气溶胶平台：桥穿心莲内酯输送与临床翻译

由于粘液积聚、生物膜形成和巨噬细胞的快速清除等生理障碍，有效的气溶胶给药仍然是治疗肺部疾病的一个挑战。在这里，我们开发了一种可吸入的蜂窝状微球（HCLplga-Ab）气溶胶平台，使用fda批准的聚乳酸-羟基乙酸（PLGA）和一种成孔剂。该平台将穿心术内酯（一种从中药中提取的生物活性化合物）与壳聚糖-氨溴索包裹在一起，以实现粘液渗透，顺序释放药物，并延长肺部潴留时间。大几何直径（~ 10-15 μm）与最佳气动尺寸（~ 2.57 μm）相结合，可确保肺深部沉积，同时避免肺泡巨噬细胞清除。在急性肺损伤（ALI）、细菌性肺炎（肺炎克雷伯菌）和真菌性肺炎（白色念珠菌）的小鼠模型中，HCLplga-Ab表现出增强的黏液渗透和生物膜破坏，肺部药物潴留均匀且延长，炎症和病原体负担显著减轻。这个多功能平台将传统医学与现代气溶胶技术相结合，为呼吸系统疾病和临床翻译提供了一个有前途的解决方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.