Celecoxib Microparticles for Inhalation in COVID-19-Related Acute Respiratory Distress Syndrome

Area of Science:

• Pharmacology
• Biotechnology
• Respiratory Medicine

Background:

• Inhalation therapy is a promising route for treating respiratory disorders, particularly those involving cytokine storms like COVID-19.
• Cytokine storms, driven by macrophage-released cytokines, are key to COVID-19 pathogenesis and can be targeted by anti-inflammatory drugs such as celecoxib (CXB).

Purpose of the Study:

• To develop celecoxib (CXB)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) for inhaled therapy.
• To ensure these MPs are suitable for internalization by alveolar macrophages and possess anti-inflammatory properties.

Main Methods:

• PLGA microparticles were prepared with 5% and 10% initial celecoxib percentages (MP-C1 and MP-C2).
• Particle size, encapsulation efficiency, in vitro drug release, macrophage uptake (using fluorescein-loaded MPs), cytotoxicity, and anti-inflammatory activity (measuring IL-1, IL-6, TNF-α) were evaluated.

Main Results:

• Microparticles exhibited a mean size of approximately 5 µm, suitable for macrophage uptake, with an encapsulation efficiency exceeding 89%.
• In vitro release of CXB was prolonged (>40 and >70 days for MP-C1 and MP-C2, respectively).
• Macrophage uptake was confirmed, and CXB-loaded MPs showed no cytotoxicity; they effectively reduced inflammatory mediator gene expression.

Conclusions:

• Developed CXB-loaded PLGA microparticles are suitable for inhaled delivery and macrophage internalization.
• The microparticles offer prolonged drug release and demonstrate potent anti-inflammatory effects, supporting their potential in treating cytokine storm-related respiratory conditions.