Pulmonary delivery of therapeutic proteins based on zwitterionic chitosan-based nanocarriers for treatment on bleomycin-induced pulmonary fibrosis

摘要

Nanoparticle-based pulmonary delivery of protein therapeutics provides a promising approach for improving protein bioavailability to treat either local or systemic diseases, however high -efficient nanocarrier is a great challenge. Here, biomimetic phosphorylcholine-chitosan nanoparticles (PCCs-NPs) taking advantages of both zwitterionic phosphorylcholine and chitosan were developed as a pulmonary protein delivery platform. msFGFR2c, a potential therapeutic protein for lung fibrosis as model was loaded into PCCs-NPs via ionic gelation. The obtained msFGFR2c/PCCs-NPs inhibited a-SMA expression in fibroblasts induced by TGF-131, slightly more effective than naked msFGFR2c. After orotracheal administration to bleomycin-induced pulmonary fibrosis model rats, msFGFR2c/PCCs-NPs resulted in a significant antifibrotic efficacy, with reduction in inflammatory cytokines and a-SMA expression, remarkable attenuation of lung fibrosis score and collagen deposition, and significant increase in survival rate, while naked msFGFR2c exhibited a poor efficacy. The in vitro and in vivo results strongly indicated that PCCs-NPs may be a promising nanocarrier for pulmonary protein delivery. (C) 2019 Elsevier B.V. All rights reserved.