Therapeutic advantage of inhaled tacrolimus-bound albumin nanoparticles in a bleomycin-induced pulmonary fibrosis mouse model.
Tacrolimus (Tac) is an immunosuppressant that inhibits translocation of nuclear factor of activated T cells and has therapeutic potential for pulmonary fibrosis. Here, we investigated the therapeutic efficacy of a sustained-release type inhaled Tac formulation for treating bleomycin-induced pulmonary fibrosis. Inhalation has many meaningful advantages over injections, such as improved patient compliance, safety, and therapeutic effect. To this end, we fabricated inhalable albumin nanoparticles with bound Tac (Tac Alb-NPs) at a daily therapeutic dose (60 μg/mouse) using a high-pressure homogenizer via nanoparticle albumin-bound technology. The Tac Alb-NPs were spherical, ∼ 182.1 ± 28.5 nm in size, with a zeta potential of -34.5 ± 0.3 mV, and the Tac incorporation efficiency was as high as ∼ 85.3%. The bound tacrolimus was released gradually from Tac Alb-NPs for ∼ 24 h, which was sufficient time for pulmonary delivery. Most of all, the inhaled Tac Alb-NPs displayed remarkable anti-fibrotic efficacy in mice with bleomycin-induced pulmonary fibrosis, which was much better than the efficacy resulting from intraperitoneal administration of Tac (60 μg/mouse) based on histopathological results (hematoxylin and eosin and Masson's trichrome staining). Furthermore, the inhaled Cy5.5-labelled Tac Alb-NPs were visualized throughout the lungs of mice for ∼ 48 h, indicating direct exposure to fibrotic tissues in lung lesions. In conclusion, Tac Alb-NPs offer great potential as an inhalation delivery formulation for treating pulmonary fibrosis. Additionally, these NPs would be particularly useful as an effective and safe prototype for delivering practically insoluble therapeutic agents into the lungs.
['Seo|Jisoo|J|', 'Lee|Changkyu|C|', 'Hwang|Ha Shin|HS|', 'Kim|Bomi|B|', 'Thao|Le Quang|le Q|', 'Lee|Eun Seong|ES|', 'Oh|Kyung Taek|KT|', 'Lim|Jong-Lae|JL|', 'Choi|Han-Gon|HG|', 'Youn|Yu Seok|YS|']
D000280:Administration, Inhalation D000418:Albumins D000818:Animals D000963:Antimetabolites D001761:Bleomycin D002626:Chemistry, Pharmaceutical D016503:Drug Delivery Systems D006909:Hydroxyproline D007166:Immunosuppressive Agents D008168:Lung D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D053758:Nanoparticles D011658:Pulmonary Fibrosis D016559:Tacrolimus
Inhalation Albumin nanoparticles Pulmonary fibrosis Tacrolimus Bleomycin-induced fibrosis model