Therapeutic advantage of inhaled tacrolimus-bound albumin nanoparticles in a bleomycin-induced pulmonary fibrosis mouse model

Pulmonary Pharmacology & Therapeutics
Jisoo SeoYu Seok Youn

Abstract

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 trichr...Continue Reading

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Citations

Dec 21, 2017·Expert Opinion on Drug Delivery·Hanan Al-LawatiAfsaneh Lavasanifar
Apr 23, 2019·The Journal of International Medical Research·Jianfeng XuZhenyu Yu
Apr 22, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Moez GhummanJyothi U Menon

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