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Biol Pharm Bull ; 42(2): 273-279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30713258

RESUMO

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.


Assuntos
Hepatócitos/metabolismo , Sulfeto de Hidrogênio/administração & dosagem , Fígado/metabolismo , Pró-Fármacos/administração & dosagem , Soroalbumina Bovina/administração & dosagem , Animais , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Sulfeto de Hidrogênio/química , Fígado/efeitos dos fármacos , Masculino , Camundongos , Pró-Fármacos/química , Células RAW 264.7 , Albumina Sérica/administração & dosagem , Albumina Sérica/química , Soroalbumina Bovina/química
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