Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles
- Authors
- Lee, Changkyu; Seo, Jisoo; Hwang, Ha Shin; Thao, Le Quang; Lee, Seunghyun; Lee, Eun Seong; Lee, Eun Hee; Choi, Han-Gon; Youn, Yu Seok
- Issue Date
- Mar-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://scholarworks.bwise.kr/erica/handle/2021.sw.erica/14183
- 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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