Intratracheal instillation of chitosan-coated formononetin-loaded porous microspheres prolongs lung retention and improves the treatment in bleomycin-induced pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung lesion, which is called a "tumor-like disease". Previous studies have confirmed that intratracheal instillation of formononetin-loaded porous microspheres (FMN-PLGA-MSs) can effectively improve bleomycin-induced pulmonary fibrosis. However, the poor lung retention of FMN-PLGA-MSs reduces the therapeutic efficacy of the FMN. Building on this foundation, this study prepared chitosan-coated formononetin porous microspheres (CS-FMN-PLGA-MSs) to enhance the FMN lung retention by leveraging the bioadhesive properties of chitosan. It is expected to prolong the action time of formononetin in lung tissues and enhance the therapeutic efficacy for pulmonary fibrosis. The study results showed that, compared to FMN-PLGA-MSs, CS-FMN-PLGA-MSs could be better taken up by MLG cells and NIH-3T3 cells. In vivo imaging demonstrated that CS-FMN-PLGA-MSs had a prolonged lung retention time, lasting up to 48 h. CS-FMN-PLGA-MSs exhibited a greater deposition in the regions of lung tissue compared to FMN-PLGA-MSs. The in vivo efficacy results in bleomycin-induced pulmonary fibrosis mice showed that, compared to FMN-PLGA-MSs, CS-FMN-PLGA-MSs had a higher anti-pulmonary fibrosis efficacy, significantly reducing hydroxyproline levels in fibrotic lung tissues, decreasing the extent of pulmonary fibrosis, and improving lung function. CS-FMN-PLGA-MSs provide a new reference for the treatment of pulmonary fibrosis.