title: Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles.
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 (-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 μg/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 μg/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.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Republic of Korea.
authors.forename: Changkyu
authors.initials: C
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Republic of Korea.
authors.forename: Jisoo
authors.initials: J
authors.lastname: Seo
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Republic of Korea.
authors.forename: Ha Shin
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Republic of Korea.
authors.forename: Le Quang
authors.initials: LQ
authors.lastname: Thao
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Republic of Korea.
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea.
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Republic of Korea. Electronic address: ysyoun@skku.edu.
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001761:Bleomycin; D048271:Chitosan / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D055672:Static Electricity; D013499:Surface Properties; D016559:Tacrolimus / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D014961:X-Ray Diffraction
chemical_list: D000336:Aerosols; D001761:Bleomycin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen; D048271:Chitosan; D006909:Hydroxyproline; D016559:Tacrolimus
keywords: Chitosan; Inhalation; PLGA nanoparticle; Pulmonary fibrosis; Tacrolimus