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

Authors
Lee, ChangkyuSeo, JisooHwang, Ha ShinThao, Le QuangLee, SeunghyunLee, Eun SeongLee, Eun HeeChoi, Han-GonYoun, Yu Seok
Issue Date
3월-2016
Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Keywords
Tacrolimus; PLGA nanoparticle; Chitosan; Pulmonary fibrosis; Inhalation
Citation
BIOMEDICINE & PHARMACOTHERAPY, v.78, pp.226 - 233
Indexed
SCIE
SCOPUS
Journal Title
BIOMEDICINE & PHARMACOTHERAPY
Volume
78
Start Page
226
End Page
233
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/89447
DOI
10.1016/j.biopha.2016.01.027
ISSN
0753-3322
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.
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