[Studies on 5-FU/PEG-PBLG nano-micelles: preparation, characteristics, and drug releasing in vivo].
OBJECTIVE
5-Fluorouracil (5-FU) belongs to antimetabolic anticancer drugs and its half-life time in vivo is only about 5 minutes. Continuous infusion (48 hours,72 hours,28 days) was commonly used to maintain long-time steady-state concentration (Css). So it is necessary to exploit new slow-release system for 5-FU. This article was designed to investigate the preparation technique,shape characteristics, and drug releasing characteristics in vivo of 5-FU loaded core-shell type nanoparticles which were made by biodegradable amphiphlic poly (ethylene glycol)-poly (gamma-benzyl-L-glutamate)(PEG-PBLG).


METHODS
The PEG-PBLG nano-micelles were prepared by diafiltration method. Its morphology was observed by transmission electron microscopy and scan electron microscopy. Encapsulating efficiency of 5-FU was determined by ultraviolet spectrophotometry. The 5-FU releasing characteristics from nano-micelles in vivo were investigated by high-performance liquid chromatography (HPLC).


RESULTS
5-FU loaded PEG-PBLG copolymer nano-micelles (5-FU/PEG-PBLG) was of round or ellipsic shape. The diameter of the micelles was 180-250 nm; the size of drug storeroom was about 200 nm and the thickness of hydrophilic zone was about 30 nm. The entrapment efficiency was (29.5+/-0.015)%. In control group, 5-FU is one-compartment in vivo; its half-life was 5.3 minutes; the maximum plasma concentration (C(max)) was 17047.3 microg/L; T(max) was the time of attaining C(max) of the end of infusion; the area under the plasma concentration-time curve (AUC) was 6263.7 microg/L x min. However, the model of nano-micelles in vivo was typical release-drug of nano-micelles namely abrupt release-slow release; its t(1/2) was 63.2 minutes; C(max) was 4563.5 microg/L; T(max) was 1.25 hours; AUC was 5794.5 microg/Lxmin. Compared with 5-FU preparation, T(max) of 5-FU/PEG-PBLG was longer (P< 0.01);C(max) was lower (P< 0.01);t(1/2) was longer (P< 0.01); AUC was similar (P >0.01).


CONCLUSIONS
The 5-FU/PEG-PBLG nano-micelles can change the pharmacokinetics of 5-FU, prolonging the circulation time in vivo and make a slow release.
Li
Su
S
Department of Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, PR China.
Jiang
Wen-Qi
WQ
Wang
An-Xun
AX
Guan
Zhong-Zhen
ZZ
Pan
Shi-Rong
SR
D000818:Animals; D019540:Area Under Curve; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008823:Micelles; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011099:Polyglutamic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D011817:Rabbits
D008823:Micelles; C003172:poly-gamma-benzyl-L-glutamate; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D005472:Fluorouracil