Biological and Pharmaceutical Bulletin

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Volume 42 (2019) Issue 2 Pages 273-279

Hepatic and Intrahepatic Targeting of Hydrogen Sulfide Prodrug by Bioconjugation

Kosuke Sakai, Hidemasa Katsumi, Kentaro Kamano, Kiyo Yamauchi, Ayuko Hajima, Masaki Morishita, Toshiyasu Sakane, Akira Yamamoto

Hydrogen sulfide (H₂S) is an endogenous gaseous transmitter known to play an important role in biological functions. For the hepatic and intrahepatic targeting of H₂S prodrug at the cellular level, we developed two types of sulfo-albumins, in which five sulfide groups (source of H₂S) were covalently bound to succinylated (Suc) or galactosylated (Gal) bovine serum albumin (BSA). Sulfo-BSA-Suc and polyethylene glycol (PEG)-Sulfo-BSA-Gal, both released H₂S in the 5 mM glutathione solution, but not in the plasma. Sulfo-BSA-Suc and PEG-Sulfo-BSA-Gal were taken up by RAW264.7 cells (mouse macrophage-like cells) and Hep G2 cells (human hepatocellular carcinoma cells), respectively, and H₂S was released. These results indicate that Sulfo-BSA-Suc and PEG -Sulfo-BSA-Gal selectively released H₂S intracellularly. In a biodistribution study, up to 80% of ¹¹¹In-labeled Sulfo-BSA-Suc and PEG-Sulfo-BSA-Gal rapidly accumulated in the liver, 30 min after intravenous injection in mice. Furthermore, ¹¹¹In-labeled Sulfo-BSA-Suc and PEG-Sulfo-BSA-Gal predominantly accumulated in liver nonparenchymal (endothelial cells and Kupffer cells) and parenchymal cells (hepatocytes), respectively. These findings suggest that targeted delivery of H₂S prodrug to a specific type of liver cells was successfully achieved by bioconjugation.

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The delivery of hydrogen sulfide (H2S) to liver is expected for the treatment of hepatic diseases. K. Sakai et al. developed two types of sulfo-albumins, macromolecular H2S prodrugs, for hepatic and intrahepatic targeting of H2S. Sulfide groups (source of H2S) were covalently bound to succinylated (Suc) and galactosylated (Gal) bovine serum albumin (BSA) for targeted delivery of H2S to hepatic nonparenchymal cells and parenchymal cells, respectively. Their results demonstrated targeted delivery of H2S prodrug to a specific type of liver cells using the chemical modification of targeting ligands.

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2019 Volume 42 Issue 2

Optimization of Individual Pharmacotherapy Based on Multiple Evaluations of Patient Data Takafumi Naito
A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants Jiangang Chen, Wenfang Lu, Hao Chen, Xiaoli Bian, Guangde Yang
Effect of Ocimum basilicum, Ocimum selloi, and Rosmarinic Acid on Cerebral Vascular Damage in a Chronic Hypertension Model Elian Alegría-Herrera, Maribel Herrera-Ruiz, Rubén Román-Ramos, Alejandro Zamilpa, Mayra Alejandra Santillán-Urquiza, María Isabel Aguilar, Margarita Avilés-Flores, Macrina Fuentes-Mata, Enrique Jiménez-Ferrer
Prophylactic Treatment with Intravenous Immunoglobulin Attenuates Experimental Optic Neuritis in Mice Hiroyuki Takahashi, Sachio Okuda, Mizuho Tamura, Shintaro Kamei, Reiko Aizawa, Tsunefumi Kobayashi

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