Shaping the Future of Pulmonary Fibrosis Therapy with Inhaled Microgels

Idiopathic pulmonary fibrosis (IPF) is a devasting lung disease characterized by progressive scarring of lung tissue. As fibrosis develops, patients experience worsening shortness of breath, reduced lung capacity and ultimately respiratory failure. Current therapies for IPF rely on oral administration of pirfenidone and nintedanib, two FDA-approved drugs that slow disease progression. While effective, oral dosing requires high systematic concentrations, which often lead to gastrointestinal side effects and liver toxicity. A targeted approach that delivers these drugs directly to the lungs offers a transformative strategy.

Inhalable Microgels as a Dual-Therapy Platform

A recent study published in Bioactive Materials by Lee et al. (2024) introduces aerosolizable inhaled microgels (µGels) designed to deliver pirfenidone and nintedanib directly to the lungs.

The ~ 12 µm microgels encapsulate:

Pirfenidone-loaded liposomes
Nintedanib-loaded PLGA nanoparticles

At this diameter, the µGels are sufficiently large to evade phagocytosis by alveolar macrophages, which typically engulf particles smaller than 6 µm. At the same time, they remain small enough to reach and deposit within the deep lung. As a result, the system achieves prolonged lung retention and sustained drug release.

Proof of Concept

In a bleomycin-induced pulmonary fibrosis mouse model, the researchers compare:

Daily nanoparticle/liposome therapy
Twice-weekly inhaled µGel therapy

Despite being administered 3.5x less often, the µGel group show comparable or superior outcomes:

Reduced collagen deposition
Lower levels of fibrosis markers (α-SMA, TGF-β)
Improved survival and body weight
Restored lung tissue structure

Measuring Lung Function

To validate therapeutic benefit, lung mechanics are assessed using flexiVent and forced oscillation technique (FOT). Key parameters demonstrate that µGel therapy significantly improves lung function toward normal levels:

Parameter	Fibrotic Effect	µGel Effect
Resistance (Rrs)	↑ Increased	↓ Restored toward normal
Elastance (Ers)	↑ Stiffness	↓ Improved elasticity
Inspiratory Capacity (IC)	↓ Reduced	↑ Significantly improved
Compliance (Crs, Cst)	↓ Decreased	↑ Restored
Tissue Elastance (H)	↑ Elevated	↓ Reduced

Mice treated with inhaled µGels achieve near-normal lung function with less frequent dosing and a lower total drug amount than daily therapy.

Clinical Potential

This work highlights the potential of macrophage-evading inhaled biomaterials to improve pulmonary fibrosis therapy. By reducing the required dosing frequency from daily to only twice weekly, the approach lessens treatment burden. Localized lung delivery also minimizes systemic exposure and lowers the risk of adverse side effects. At the same time, the therapy enhances outcomes by restoring lung function and improving survival in preclinical models. The formulation is built from FDA-approved components such as PEG, albumin, PLGA and lipids, making it a biocompatible and clinically translatable platform.

Conclusion

Innovative microgel design, combined with precise lung function assessment using flexiVent, enables effective, sustained therapy for pulmonary fibrosis with fewer doses and lower drug exposure.

References

Lee, W.T., et al. (2024) Bioactive Materials, 33, 262–278. Alveolar macrophage phagocytosis-evading inhaled microgels incorporating nintedanib-PLGA nanoparticles and pirfenidone-liposomes for improved treatment of pulmonary fibrosis.

Empowering researchers

Welcome to SCIREQ’s knowledge center. You can find everything from software registration to document downloads to complete list of SCIREQ publications in this section. Everything you need to get the most out of your SCIREQ system.