Inhalable Food-Grade MOFs Loaded Gas Messenger for Acute Lung Injury Treatment by Pulmonary Delivery.

Area of Science:

• Biomedical Engineering
• Materials Science
• Pharmacology

Background:

• Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe conditions with high mortality rates.
• Current treatments like corticosteroids have limited efficacy due to poor lung drug concentration.
• There is a need for novel therapeutic strategies targeting the lungs directly.

Purpose of the Study:

• To develop a novel dry powder inhaler (DPI) platform for targeted sulfur dioxide (SO2) delivery to the lungs for ALI treatment.
• To evaluate the physicochemical properties, lung-targeting capability, and therapeutic efficacy of the developed SO2-loaded γCD-MOF.
• To investigate the underlying anti-inflammatory mechanisms of the SO2-delivery system.

Main Methods:

• Fabrication of a cholesterol-modified γ-cyclodextrin-based metal-organic framework (CHS-CD-MOF) loaded with SO2 (CHS-CD-MOF@SO2).
• Assessment of aerodynamic characteristics (FPF, GSD, MMAD) and storage stability.
• In vivo lung targeting confirmed using rhodamine B fluorescence imaging.
• In vitro SO2 release kinetics and simulated lung fluid permeability.
• Evaluation of anti-inflammatory effects in an ALI mouse model by measuring pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and assessing lung histopathology.
• Comparison of therapeutic efficacy with dexamethasone (DXMS).

Main Results:

• CHS-CD-MOF@SO2 exhibited excellent aerodynamic properties (FPF 40%, GSD 1.61, MMAD 4.8 μm) for effective lung deposition.
• In vivo imaging confirmed superior lung-targeting capability of CHS-CD-MOFs.
• Rapid and efficient release of SO2 (92.3% in 5 min) and high permeability (85% in 30 min) in simulated lung fluid.
• Significant reduction in pro-inflammatory factors (TNF-α, IL-1β, IL-6) by regulating P38 and NF-κB pathways in ALI mice.
• Improved lung tissue hydration and reduced neutrophil infiltration, with therapeutic outcomes comparable or superior to dexamethasone.

Conclusions:

• The developed CHS-CD-MOF@SO2 platform is a promising strategy for targeted lung delivery of SO2 via DPI for ALI treatment.
• This novel gas messenger platform demonstrates significant anti-inflammatory effects and therapeutic potential, offering an alternative to conventional therapies.
• The study highlights a novel approach for treating ALI using advanced materials for efficient drug delivery.