Physicochemical, tissue distribution, and vasodilation characteristics of nitrosated serum albumin: delivery of nitric oxide in vivo.
Conjugates of nitric oxide (NO) to serum albumins are candidates for controlled delivery of NO in vivo, but their physicochemical and tissue distribution characteristics have hardly been examined yet. In this study, to achieve its in vivo delivery, bovine serum albumin (BSA) was reacted with sodium nitrite to obtain NO-BSA, which had 0.25-0.28 molecules of S-nitrosothiol/BSA. In addition to cystein, other amino acid residues were modified by the reaction. The conjugation had no significant effect on the molecular weight, but reduced the electric charge and induced reversible changes in the secondary structure of BSA. After intravenous injection in mice at a dose of 1 mg/kg, 111In-NO-BSA slowly disappeared from plasma in a similar manner to 111In-BSA, but showed greater accumulation in the liver and kidney. NO-BSA induced a transient decrease in arterial pressure after intravenous injection in rats at a dose of 100 mg/kg, and significantly increased the distribution of 111In-BSA to the lung in mice. These results indicate that NO is released from NO-BSA shortly after injection, and this NO decreases blood pressure and increases the distribution of macromolecules to the lung. These findings provide useful basic information for designing macromolecular NO donors able to achieve controlled delivery of NO.
Departments of Drug Delivery Research. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Hidemasa
H
Katsumi
Makiya
M
Nishikawa
Shen-Feng
SF
Ma
Fumiyoshi
F
Yamashita
Mitsuru
M
Hashida
D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015538:Nitrosation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D012709:Serum Albumin; D009569:Nitric Oxide