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Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles

Title
Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles
Author
최한곤
Keywords
Tacrolimus; PLGA nanoparticle; Chitosan; Pulmonary fibrosis; Inhalation
Issue Date
2016-03
Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Citation
BIOMEDICINE & PHARMACOTHERAPY, v. 78, Page. 226-233
Abstract
Pulmonary fibrosis is a chronic lung disease characterized by inflammation and collagen deposition, with an estimated mortality rate exceeding 70%. Here, we evaluated the therapeutic effectiveness of inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles (chitosan TAC PLGA-NPs) in a bleomycin-induced pulmonary fibrosis mouse model. Chitosan TAC PLGA-NPs were fabricated using an o/w emulsification diffusion method, and uncoated TAC PLGA-NPs and chitosan TAC PLGA-NPs were spherical with approximate diameters of 320 and 441 nm, respectively. The zeta potential of chitosan TAC PLGA-NPs (+ 13.6 mV) was increased significantly by chitosan-coating versus uncoated TAC PLGA-NPs (similar to 28.3 mV). The incorporation efficiency of tacrolimus was 37.7%, and the tacrolimus was gradually released until about 5 day. Direct inhalation of chitosan TAC PLGA-NPs (TAC 180 mg/mouse) twice a week produced marked anti-fibrotic efficacy in mice with bleomycin-induced pulmonary fibrosis, which was much better than the efficacy resulting from daily oral administration (TAC 300 mg/mouse) on the basis of hematoxylin/eosin and Masson's trichrome staining assessments. Imaging of lung deposition showed that chitosan TAC PLGA-NPs were located well in the lungs and gradually faded over 96 h. The pulmonary delivery of tacrolimus could be therapeutically efficacious for treating pulmonary fibrosis. TAC-loaded PLGA nanoparticles should be considered to be an efficient sustained-release type inhalation system that reduces administration frequency and relevant side effects. (C) 2016 Elsevier Masson SAS. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0753332215302389http://hdl.handle.net/20.500.11754/50258
ISSN
0753-3322; 1950-6007
DOI
10.1016/j.biopha.2016.01.027
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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