Chronic obstructive pulmonary disease (COPD) is a lung disease with an incidence expected to rise in the coming years. Beyond their hypolipidemic effects, statins, including atorvastatin (ATV), exhibit pleiotropic activities, and several studies have reported their efficacy in treating COPD and its exacerbations. This study aims to develop and characterize a spray-dried high-content (>90%) ATV powder for inhalation, also evaluating its effects in BEAS-2B lung epithelial cells. ATV was co-spray-dried with leucine resulting in a production yield of approximately 50%. SEM images revealed small (~1–2 μm) and spherical particles with an irregular surface. Aerodynamic evaluation using a multi-stage liquid impinger (MSLI) showed a respirable fraction between 41 and 52%, emitted fractions of 58–66%, and mass median aerodynamic diameters (MMAD) of 2.6–3.0 μm. To facilitate the dosing for in vitro studies, a blend of the spray-dried ATV with lactose and magnesium stearate was prepared. LPS-stimulated BEAS-2B cells were used to investigate the antioxidant and anti-inflammatory potential of ATV. ATV solution and, more efficiently, the spray-dried ATV blend reduced the extracellular H2O2 and IL-6 levels. Excipients alone showed no anti-inflammatory effect. Real-time PCR showed that both the ATV solution and ATV blend downregulated IL-6 expression whereas TGF-β, PPAR-γ, and PLIN-2 were upregulated. In conclusion, an inhalable ATV dry powder was developed, demonstrating strong anti-inflammatory and antioxidant effects in LPS-treated BEAS-2 cells.
Development of an inhalable atorvastatin powder and its anti-inflammatory effects in human lung cells
Mancini, Lorenzo;Di Sante, Gabriele;Galli, Francesco;Ricci, Maurizio;Bartolini, Desirée;Schoubben, Aurelie
2026
Abstract
Chronic obstructive pulmonary disease (COPD) is a lung disease with an incidence expected to rise in the coming years. Beyond their hypolipidemic effects, statins, including atorvastatin (ATV), exhibit pleiotropic activities, and several studies have reported their efficacy in treating COPD and its exacerbations. This study aims to develop and characterize a spray-dried high-content (>90%) ATV powder for inhalation, also evaluating its effects in BEAS-2B lung epithelial cells. ATV was co-spray-dried with leucine resulting in a production yield of approximately 50%. SEM images revealed small (~1–2 μm) and spherical particles with an irregular surface. Aerodynamic evaluation using a multi-stage liquid impinger (MSLI) showed a respirable fraction between 41 and 52%, emitted fractions of 58–66%, and mass median aerodynamic diameters (MMAD) of 2.6–3.0 μm. To facilitate the dosing for in vitro studies, a blend of the spray-dried ATV with lactose and magnesium stearate was prepared. LPS-stimulated BEAS-2B cells were used to investigate the antioxidant and anti-inflammatory potential of ATV. ATV solution and, more efficiently, the spray-dried ATV blend reduced the extracellular H2O2 and IL-6 levels. Excipients alone showed no anti-inflammatory effect. Real-time PCR showed that both the ATV solution and ATV blend downregulated IL-6 expression whereas TGF-β, PPAR-γ, and PLIN-2 were upregulated. In conclusion, an inhalable ATV dry powder was developed, demonstrating strong anti-inflammatory and antioxidant effects in LPS-treated BEAS-2 cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
