Tumor accumulation of gadolinium in lipid-nanoparticles intravenously injected for neutron-capture therapy of cancer.
Gadolinium-incorporating lipid-nanoemulsions (Gd-nanoLE) for neutron-capture therapy were prepared. As a more convenient administration route than the intraperitoneal (i.p.) injection previously reported, the intravenous (i.v.) injections in tumor-bearing hamsters were carried out at an administration volume of 1 ml, which was the maximum tolerable injection volume of an i.v. injection and half that of an i.p. injection. When the standard-Gd-nanoLE of 1.5 mgGd/ml was administered, the absolute bioavailability in the i.p. injection was 57%, probably resulting from incomplete absorption from the peritoneal cavity into the blood stream. The biodistribution data revealed that the i.v. injection had three advantages over the i.p. injection, namely, a faster and higher accumulation of Gd-nano LE, and a more extended retention time in the tumor. Two i.v. injections of the standard-Gd-nanoLE with a 24h interval doubled the tumor accumulation of Gd, resulting in 49.7 microg Gd/g wet tumor 12h after administration. By using a twofold Gd-enriched formulation (High-Gd-nanoLE) of 3.0 mgGd/ml in the repeated administration schedule, the accumulation was doubled again, reaching 101 microg Gd/g wet tumor. This level was comparable to the maximum level in the single i.p. injection previously reported. These results demonstrated that i.v. injection could be an alternative to i.p. injection as an administration route.
Watanabe
Tetsuya
T
Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University, Kobe, Japan.
Ichikawa
Hideki
H
Fukumori
Yoshinobu
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D006224:Cricetinae; D004334:Drug Administration Schedule; D004337:Drug Carriers; D004655:Emulsions; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008055:Lipids; D008546:Melanoma, Experimental / Q000378:metabolism*; D036103:Nanotechnology; D017247:Neutron Capture Therapy; D010316:Particle Size; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D005682:Gadolinium