Inhalable iguratimod-loaded nanostructured lipid carriers for asthma-chronic obstructive pulmonary disease overlap management.

Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a chronic inflammatory airway condition that presents with features of both asthma and COPD, complicating its treatment and management. In this study, the potential of iguratimod-loaded nanostructured lipid carriers (IGU-NLCs) as an inhalable therapy for ACO was investigated. IGU-NLCs were formulated and characterized using Fourier-transform infrared, X-ray diffraction, thermogravimetric - differential scanning calorimetry, field emission scanning electron microscopy, and particle size analysis. The formulation demonstrated favorable physicochemical stability and nanoscale particle size distribution. IGU-NLCs demonstrated good cytocompatibility and minimal reactive oxygen species induction at 10 μg/mL in vitro, supporting their suitability for safe pulmonary delivery. An in vivo ACO model was induced by papain/cigarette smoke exposure, followed by treatment with plain IGU and IGU-NLCs via inhalation, to evaluate their therapeutic effects on oxidative stress, inflammation, and lung function. X-ray and ECG analyses revealed that IGU-NLCs more effectively reversed the airway obstruction and cardiac alterations induced by papain/cigarette smoke exposure. Histopathologic analysis showed significant improvement in lung architecture. Moreover, immunohistochemistry for CD68+ revealed reduced macrophage infiltration, indicating an anti-inflammatory effect. Overall, this study demonstrates that nebulized IGU-NLCs offer a noninvasive, targeted, and effective approach to mitigate ACO pathology, highlighting their potential for clinical translation in respiratory therapeutics. SIGNIFICANCE STATEMENT: Asthma-chronic obstructive pulmonary disease overlap lacks effective therapies because of its complex pathophysiology. This study repurposed iguratimod using nanostructured lipid carriers for inhalation, which reduced inflammation, oxidative stress, and lung damage in vivo, highlighting a novel, targeted strategy for this overlapped disease.