In Vitro and In Vivo Evaluation of Hydrophilic C60(OH)10/2-Hydroxypropyl-β-cyclodextrin Nanoparticles as an Antioxidant.
The objective of this study was to assess the antioxidant ability of C60(OH)10/2-hydroxypropyl-β-cyclodextrin (HP-β-CD) nanoparticles, by comparing their scavenging ability for reactive nitrogen species, their cytoprotective effects under conditions of oxidative stress, and their therapeutic effects against diseases that are induced by oxidative stress. The C60(OH)10/HP-β-CD nanoparticles had a higher scavenging activity against nitric acid and peroxynitrite (ONOO(-)) than the other antioxidants such as ascorbic acid, trolox, and edaravone. The cytoprotective effect of C60(OH)10/HP-β-CD nanoparticles was examined on HeLa and HepG2 cells by monitoring the percentage of cell death induced by H2O2. Treatment with C60(OH)10/HP-β-CD nanoparticles resulted in an increase in cell viability, due to the suppression of the oxidative stress. Furthermore, the nanoparticles had a high cytoprotective effect, compared with other polyhydroxylated C60 (C60(OH)24 and C60(OH)40). The C60(OH)10/HP-β-CD nanoparticles were intravenously administered to mice with a liver injury induced by an over dose of acetaminophen. Levels of alanine transaminase and aspartate transaminase were essentially the same as those of normal mice and the survival rate was also prolonged by the intravenous administration of the C60(OH)10/HP-β-CD nanoparticles. The results indicate that C60(OH)10/HP-β-CD nanoparticles are a promising antioxidant for use in the treatment of diseases caused by oxidative stresses.
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Daisuke
D
Iohara
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Yoshitaka
Y
Umezaki
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Makoto
M
Anraku
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Kaneto
K
Uekama
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan. Electronic address: fhira@ph.sojo-u.ac.jp.
Fumitoshi
F
Hirayama
D000073738:2-Hydroxypropyl-beta-cyclodextrin / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D037741:Fullerenes / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000737:chemistry; D026361:Reactive Nitrogen Species
D000975:Antioxidants; D016166:Free Radical Scavengers; D037741:Fullerenes; D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D009569:Nitric Oxide
antioxidants; colloid; cyclodextrins; free radicals; nanoparticles