Inhalable Nanotechnology-Based Drug Delivery Systems for the Treatment of Inflammatory Lung Diseases

Abstract

This review explores recent advancements in inhaled nanoparticle formulations and inhalation devices, with a focus on various types of nanoparticles used for inhalation to treat inflammatory lung diseases and the types of devices used in their delivery. Medical nebulizers have been found to be the most appropriate type of inhalation devices for the pulmonary delivery of nanoparticles, since formulations can be prepared using straightforward techniques, with no need for liquefied propellants as in the case of pressurized metered dose inhalers (pMDIs), or complicated preparation procedures as in the case of dry powder inhalers (DPIs). We demonstrated examples of how formulations should be designed considering the operation mechanism of nebulizers, and how an interplay of factors can affect the aerosol characteristics of nanoparticle formulations. Overall, nanoparticle-based formulations offer promising potential for the treatment of inflammatory lung diseases due to their unique physicochemical properties and ability to provide localized drug delivery in the lung following inhalation.

Keywords: drug delivery; inflammatory lung disorders; inhalation devices; nanoparticles.

Figure 1

Schematic illustration of the pulmonary barriers confronting the particle during its journey to the respiratory zone in the respiratory system. The airways are lined with different types of cells, each having their own unique function. This involves the epithelial cells of the airways, the goblet cells that produce mucus, the ciliated cells that expel mucus, and the basal cells that have a role in tissue repair and regenerating respiratory epithelium. The diagram also demonstrates the corresponding diameter of each section of the respiratory system and the eligible sizes for particles to deposit. Created in BioRender https://BioRender.com/qlbk9ns (accessed on 2 June 2025).

Figure 2

A schematic presentation for the design of (a) pressurized metered dose inhaler (pMDI), (b) single-unit dose DPI, (c) multi-unit dose DPI, and (d) soft mist inhaler (SMI). Created in BioRender.

Figure 3

A schematic presentation demonstrating the general design of the three types of nebulizer: (a) jet nebulizer, (b) ultrasonic nebulizer, and (c) mesh nebulizer. Created in BioRender.

Figure 4

A schematic diagram of nanoparticle formulations investigated for the treatment of inflammatory diseases. Created in BioRender.

Figure 5

Histopathology of lung sections using hematoxylin and eosin (H&E) stain, after delivery to BALB/c mice using an ultrasonic nebulizer. Arrows indicate inflammatory cell infiltration, arrowheads represent epithelium, and stars depict edema across all images. (A) Phosphate buffered saline (control group) depicts edema with severe perivascular and peribronchial inflammatory cell infiltration. (B) Dexamethasone positive control group shows moderate perivascular and peribronchial inflammatory cell infiltration with edema. (C) Taraxasterol group manifests edema with mild perivascular and peribronchial inflammatory cell infiltration. (D) Nano-Taraxcestrol group showcases no perivascular and peribronchial inflammatory cell infiltration with edema. (E) PEG-PLGA formulation group shows moderate perivascular and peribronchial inflammatory cell infiltration with edema. The figure was reproduced with permission from [112], Copyright Springer Nature 2024.

Figure 6

(a) Summary of the preparation of Lung-exos nanoparticle formulation. (b) TEM images of the nanoparticles of the exosomal (RFP-Exos) and liposomal (RFP-Lipos) formulations; scale bar: 50 nm. (c) The delivery of the new formulations using dry powder inhalation. (d) Retention and uptake of RFP-Exos formulation in comparison to RFP-Lipos formulation in the lung bronchial and parynchymal regions; **** represents statistical difference. Figure was reproduced with permission from [132], Copyright Elsevier 2022.

Figure 7

Schematic representation of the principle of top-down and bottom-up techniques used for the synthesis of inorganic nanoparticles. This figure was redrawn using BioRender. with permission from [167], Copyright Elsevier 2024.

Figure 8

The number of articles published using the word “inhalable nanoparticles” in their title in the PubMed database over the past 20 years. It is evident that this field is gaining more attention with time, especially during the last 15 years.

Figure 9

(a) Chitosan nanoparticles delivery using a pMDI device. (b) Scanning electron microscopy (SEM) images of freeze-dried chitosan–PEG 1000 nanoparticles prior to delivery. (c) Scanning electron microscopy (SEM) images of chitosan–PEG 1000 nanoparticles post actuation using the pMDI. (d) fine particle fraction percentages of the different chitosan formulations. Figure was reproduced using BioRender with permission from [188]. Copyright Elsevier 2012.