Organ distribution of 5-fluorouracil loaded gelatine microspheres in mice.
The aim of this study was to investigate the organ distribution characteristics of 5-fluorouracil (5-Fu) loaded crosslinked gelatine microspheres (5-Fu-MS) after intravenous (i.v.) injection compared to 5-Fu solution in mice, and to evaluate the targetability of 5-Fu-MS. The concentrations of 5-Fu in mice plasma, heart, liver, lung, kidney, spleen and brain were determined by HPLC. The parameters drug targeting index C(e), time-averaged relative drug exposure values r(e), drug targeting efficiency t(e), and drug distributed to target-tissue (%) were used to evaluate the targetability of the 5-Fu-MS delivery system. The results showed that the concentration of 5-Fu in the lung was significantly higher than after application of 5-Fu solution, and that the maximum concentration of 5-Fu, 72.8 microg x g organ(-1), was reached in the lung at 15 min after i.v. administration. As for 5-Fu-MS, r(e) was calculated to be 2.2, and t(e) was considerably higher than after application of 5-Fu in solution. Furthermore, the percentage of drug distributed to the lung was 2 times as high as after application in solution. Accordingly, 5-Fu-MS were capable of effectively delivering 5-Fu to the lung and possessed specific targetability towards the lung compared to 5-Fu solution.
Hao
Xiuhua
X
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Cheng
Gang
G
Zou
Meijuan
M
Sun
Jin
J
Cui
Fude
F
D000465:Algorithms; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems; D005079:Excipients; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005780:Gelatin; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D019999:Pharmaceutical Solutions; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D003432:Cross-Linking Reagents; D005079:Excipients; D007202:Indicators and Reagents; D019999:Pharmaceutical Solutions; D005780:Gelatin; D005472:Fluorouracil