Inhalation treatment of idiopathic pulmonary fibrosis with curcumin large porous microparticles

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with high mortality and poor prognosis. Curcumin shows anti-inflammatory effect by suppressing pro-inflammatory cytokines and inhibiting NF-κB mediated inflammation. Here, we developed inhalable curcumin-loaded poly(lactic-co-glycolic)acid (PLGA) large porous microparticles (LPMPs) for the treatment of IPF. Curcumin LPMPs were rough and loose particles with many pores on the surfaces and channels in the inner spaces. The mean geometric diameter of them was larger than 10 µm while the aerodynamic diameter was only 3.12 µm due to their porous structures. They showed a fine particle fraction (FPF) <4.46 μm of 13.41%, 71% cumulative release after 9 h, and more importantly, they avoided uptake by alveolar macrophages. Therefore, most of released curcumin had opportunities to enter lung tissues. Rat pulmonary fibrosis models were established via once intratracheal administration of bleomycin. Curcumin powders and curcumin LPMPs were administered on Days 2, 7, 14, and 21. Curcumin LPMPs remarkably attenuated lung injuries, decreased hydroxyproline contents, reduced the synthesis of collagen I, and inhibited the expressions of TNF-α, TGF-β1, NF-κB p65 and MMP9. Moreover, curcumin LPMPs showed higher antifibrotic activity than curcumin powders. Curcumin LPMPs are a promising inhalable medication for the treatment of IPF.