Details

Autor(en) / Beteiligte

• Yasuda, Kengo
• Maeda, Hitoshi
• Kinoshita, Ryo
• Minayoshi, Yuki
• Mizuta, Yuki
• Nakamura, Yuka
• Imoto, Shuhei
• Nishi, Koji
• Yamasaki, Keishi
• Sakuragi, Mina
• Nakamura, Teruya
• Ikeda-Imafuku, Mayumi
• Iwao, Yasunori
• Ishima, Yu
• Ishida, Tatsuhiro
• Iwakiri, Yasuko
• Otagiri, Masaki
• Watanabe, Hiroshi
• Maruyama, Toru

Titel

Encapsulation of an Antioxidant in Redox-Sensitive Self-Assembled Albumin Nanoparticles for the Treatment of Hepatitis

Ist Teil von

• ACS nano, 2023-09, Vol.17 (17), p.16668-16681

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Hepatitis is an inflammation of the liver caused by the inadequate elimination of reactive oxygen species (ROS) derived from Kupffer cells. Edaravone is clinically used as an antioxidant but shows poor liver distribution. Herein, we report on the design of a Kupffer cell-oriented nanoantioxidant based on a disulfide cross-linked albumin nanoparticle containing encapsulated edaravone (EeNA) as a therapeutic for the treatment of hepatitis. Since the edaravone is bound to albumin, this results in a soluble and stable form of edaravone in water. Exchanging the intramolecular disulfide bonds to intermolecular disulfide bridges of albumin molecules allowed the preparation of a redox responsive albumin nanoparticle that is stable in the blood circulation but can release drugs into cells. Consequently, EeNA was fabricated by the nanoscale self-assembly of edaravone and albumin nanoparticles without the additives that are contained in commercially available edaravone preparations. EeNA retained its nanostructure under serum conditions, but the encapsulated edaravone was released efficiently under intracellular reducing conditions in macrophages. The EeNA was largely distributed in the liver and subsequently internalized into Kupffer cells within 60 min after injection in a concanavalin-A-induced hepatitis mouse. The survival rate of the hepatitis mice was significantly improved by EeNA due to the suppression of liver necrosis and oxidative stress by scavenging excessive ROS. Moreover, even through the postadministration, EeNA showed an excellent hepatoprotective action as well. In conclusion, EeNA has the potential for use as a nanotherapeutic against various types of hepatitis because of its Kupffer cell targeting ability and redox characteristics.