Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury

Area of Science:

• Pharmacology
• Respiratory Medicine
• Drug Delivery Systems

Background:

• Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) can trigger cytokine storms leading to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).
• Cepharanthine (CEP), a natural alkaloid, possesses anti-inflammatory and antiviral properties but suffers from poor oral bioavailability.
• Pulmonary administration offers a direct route to the lungs, potentially overcoming CEP's bioavailability limitations for ALI treatment.

Purpose of the Study:

• To develop and evaluate Cepharanthine dry powder inhalers (CEP DPIs) for pulmonary administration in treating acute lung injury (ALI).
• To assess the anti-inflammatory effects and efficacy of CEP DPIs in an ALI rat model.

Main Methods:

• CEP was formulated into dry powder inhalers (DPIs) using a freeze-drying method.
• Powder properties, including aerodynamic median diameter (Da) and in vitro lung deposition, were evaluated.
• An ALI rat model was induced via intratracheal hydrochloric acid injection, followed by CEP DPI administration (30 mg/kg).

Main Results:

• The developed CEP DPIs met Chinese Pharmacopoeia standards for pulmonary inhalation (Da = 3.2 μm, lung deposition = 30.26%).
• CEP DPI treatment significantly reduced pulmonary edema, hemorrhage, and inflammatory factors (TNF-α, IL-6, total protein) in ALI rats (p < 0.01).
• The anti-inflammatory action of Cepharanthine was identified as the primary mechanism for ALI treatment.

Conclusions:

• Dry powder inhalers provide direct drug delivery to the lungs, enhancing intrapulmonary utilization and efficacy of Cepharanthine for ALI.
• CEP DPIs represent a promising inhalable formulation for the treatment of acute lung injury.