Higher lung accumulation of intravenously injected organic nanotubes.
The size and shape of intravenously injected particles can affect their biodistribution and is of importance for the development of particulated drug carrier systems. In this study, organic nanotubes (ONTs) with a carboxyl group at the surface, a length of approximately 2 μm and outer diameter of 70-90 nm, were injected intravenously into tumor-bearing mice. To use ONTs as drug carriers, the biodistribution in selected organs of ONTs postinjection was examined using irinotecan, as an entrapped water-soluble marker inside ONTs, and gadolinium-chelated ONT, as an ONT marker, and compared with that of a 3 μm fluorescently labeled spherical microparticle which was similar size to the length of ONTs. It was found that for irinotecan, its active metabolite and gadolinium-chelated ONTs were highly accumulated in the lung, but to a lower level in the liver and spleen. On the other hand, microparticles deposited less in the lung and more highly in the liver. Moreover, histologic examination showed ONTs distributed more in lung tissues in part, whereas microparticles were present in blood vessels postinjection. These preliminary results support the notion of using negatively charged ONTs as intravascular carriers to maximize accumulation in the lung whilst reducing sequestration by the liver and spleen. This finding suggested that ONTs are potential carriers for lung-targeting drug delivery.
Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan. yoshie@hoshi.ac.jp
Yoshie
Y
Maitani
Yuri
Y
Nakamura
Masao
M
Kon
Emi
E
Sanada
Kae
K
Sumiyoshi
Natsuki
N
Fujine
Masumi
M
Asakawa
Masaki
M
Kogiso
Toshimi
T
Shimizu
D000818:Animals; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D000077146:Irinotecan; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D043942:Nanotubes / Q000737:chemistry*; D010316:Particle Size; D014018:Tissue Distribution
D004337:Drug Carriers; D000077146:Irinotecan; D005682:Gadolinium; D002166:Camptothecin
biodistribution; lung; microparticle; organic nanotube; particle shape