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