Chitosan Nanoparticles for Pulmonary Delivery of Curcumin/Nintedanib to Treat Pulmonary Fibrosis

Mengya Jin,1,* Jinming Liu,1,* Mengliu Shao,1 Shaoqin He,1 Yue He,2 Qingliang Yang,1 Gensheng Yang1 1College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China; 2Pharmacy Department, Zhejiang Provincial Dermatology Hospital, Huzhou, Zhejiang, 313200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yue He, Email [email protected] Gensheng Yang, Email [email protected]/Objective: Pulmonary fibrosis is a chronic, progressive lung disease with a high mortality rate. Currently, the treatment options for IPF involve the oral administration of nintedanib (NDNB); however, these therapies are hampered by low oral bioavailability. This study aimed to develop chitosan-based nanoparticles for pulmonary delivery to enhance the therapeutic effects of curcumin (Cur) and NDNB.Methods: We successfully prepared and optimized Cur-loaded chitosan nanoparticles (Cur/CS-VES NPs) and NDNB-loaded chitosan nanoparticles (NDNB/CS-PGA NPs) through a standardized process. In vitro, Calu-3 and HFL1 cells were treated to evaluate the biocompatibility of chitosan nanocarrier materials and the antifibrotic activity of drug-loaded nanoparticles, respectively. In vivo, the bleomycin-induced rat models of pulmonary fibrosis were established to study the efficacy of chitosan nanoparticles.Results: In vitro experiments indicated that the drug-loaded chitosan nanoparticles exhibited good stability and low cytotoxicity. In vivo pharmacodynamic studies revealed that, compared with oral administration of Cur or NDNB alone, the pulmonary delivery of Cur/CS-VES NPs and NDNB/CS-PGA NPs effectively inhibited the progression of pulmonary fibrosis, improved lung function, reduced levels of inflammatory factors, and mitigated pathological lesions in the lungs. These findings suggest that chitosan-based nano-particles have promising potential as pulmonary inhalation agents for the treatment of pulmonary fibrosis.Conclusion: These findings highlight the great potential of chitosan-based nanoparticles as a therapeutic strategy for treating IPF and related pulmonary fibrosis with pulmonary delivery pathways.Keywords: pulmonary drug delivery, nanoparticles, chitosan, idiopathic pulmonary fibrosis, curcumin, nintedanib