Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles |
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| Affiliation: | 1. School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Republic of Korea;2. Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea;3. College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Republic of Korea;4. College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea;1. School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Republic of Korea;2. Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea;3. College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea;1. Department of Dermatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan;2. Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan;1. MJR PharmJet GmbH, Industriestr. 1B, 66802 Überherrn, Germany;2. Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany;3. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, Saarbrücken, Germany;4. Pferdeklinik Altforweiler, Raiffeisenstraβe 100, 66802 Überherrn, Germany;1. College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-Ro, Yuseong-Gu, Daejeon 34134, Republic of Korea;2. Division of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Rangsit Center, Pathumthani 12120, Thailand;3. College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-Ro, Sangnok-Gu, Ansan 15588, Republic of Korea;1. Pharmaceutical Research & Technology Labs., Astellas Pharma Inc., 180, Ozumi, Yaizu-shi, Shizuoka 425-0072, Japan;2. Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan;3. Research Portfolio & Science, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan |
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| 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. |
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| Keywords: | Tacrolimus PLGA nanoparticle Chitosan Pulmonary fibrosis Inhalation |
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