Trehalose-stabilized micelle-in-microparticles of icariin targeting IL-4 pathway in chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory airway disorder with limited therapeutic strategies capable of addressing its underlying immunopathology. Icariin (ICA), a flavonoid with documented anti-inflammatory and antioxidant activity, exhibits mechanistic relevance to COPD pathology but is limited in clinical utility due to poor aqueous solubility and low systemic bioavailability. This study reports the development of a dry powder inhalation system comprising DSPE-PEG2000/DPPC micelle-in-microparticles stabilized with trehalose for targeted pulmonary delivery of ICA. Spray-drying produced respirable microparticles with a mass median aerodynamic diameter of 2.36 ± 0.3 µm, an emitted dose of 93 %, and a fine particle fraction of 44 %, consistent with efficient deposition in the lower respiratory tract. Physicochemical characterization confirmed ICA encapsulation in an amorphous state, with preservation of micellar structure upon rehydration, supporting formulation stability. In vitro studies demonstrated enhanced uptake of ICA-loaded micelles by RAW 264.7 macrophages and a 73 % reduction in IL-4-induced CD206 expression, indicative of inhibition of M2 macrophage polarization. These findings support the potential applicability of this inhalable system for modulating macrophage-mediated inflammation in COPD. In vivo studies are required to evaluate pharmacokinetic behaviour, pulmonary distribution, and therapeutic efficacy in validated models of chronic obstructive pulmonary disease.