In vivo biodistribution for tumor targeting of 5-fluorouracil (5-FU) loaded N-succinyl-chitosan (Suc-Chi) nanoparticles.
5-Fluorouracil-loaded N-succinyl-chitosan nanoparticles (5-FU-Suc-Chi/NP) were prepared by emulsification solvent diffusion. Biodistribution and tumor targeting were evaluated after i.v. administration of 5-Fu-Suc-Chi/NPs in Sarcoma 180-bearing mice. Also, pharmacokinetic profiles were evaluated after intravenous injection of 5-Fu-Suc-Chi/NP via the tail vein to rats. Our experimental results showed the 5-FU-Suc-Chi/NPs could be sustained at a high level in the blood for a very long time, implying its long systemic retention in the circulation. 5-FU-Suc-Chi/NPs were distributed mainly in tumors and liver, with small quantities being found in kidney and spleen. 5-FU-Suc-Chi/NPs accumulated only slightly in the heart and lung, and lowered the toxic effect of 5-FU in the heart and lung. Pharmacokinetic analysis in plasma showed the area under plasma concentration-time curve (AUC), elimination half-life (t(1/2)), and residence time (MRT) were increased 2.5-fold, 10.98-fold, and 10.8-fold for 5-FU-Suc-Chi/NP compared with that of free 5-FU, respectively. These results indicate that a long half-life in the circulation and tumor targeting of 5-FU-Suc-Chi/NPs are possible.
Department of Pharmaceutics, Shenyang Pharmaceutical University, China.
Chengyun
C
Yan
Jiwei
J
Gu
Yuzhi
Y
Guo
Dawei
D
Chen
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D001682:Biological Availability; D048271:Chitosan; D004337:Drug Carriers; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012510:Sarcoma 180 / Q000378:metabolism*; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D048271:Chitosan; D005472:Fluorouracil