Preparation and passive target of 5-fluorouracil solid lipid nanoparticles.
This work studied the intravenous injection formulation of solid lipid nanoparticles (SLNs) loaded with 5-fluorouracil (5-FU). The goal was to design longer drug residence in vivo and passive targeting nanoparticles which could improve therapeutic efficacy and reduce side-effects. Based on the optimized results of uniform design experiment, 5-FU-SLNs were prepared by multiple emulsion-ultrasonication (w/o/w). The SLNs were found to be relatively uniform in size (182.1 +/- 25.8 nm) with a negative zeta potential (-27.89 +/- 5.1 mV). The average drug entrapment efficiency and loading were 74% and 10%, respectively. Compared with the 5-FU solution (t(1/2beta), 0.593h; MRT, 0.358h) after intravenous injection to rats, the pharmacokinetic parameters of 5-FU-SLNs exhibited a longer retention time. (t(1/2beta), 4.0628h; MRT, 3.5321h). The area under curve of plasma concentration-time (AUC) of 5-FU-SLNs was 1.48 times greater than that of free drugs. The overall targeting efficiency (TE(C)) of the 5-FU-SLNs was enhanced from 13.25-20.45% in the lung and from 11.48-23.16% in kidney while the spleen distribution of 5-FU was significantly reduced as compared with that of the 5-FU solution. These results indicated that 5-FU-SLNs were promising passive targeting therapeutic agents for curing primary lung carcinoma.
Du
Bin
B
School of Pharmacy, Zhengzhou University, Zhengzhou, Henan Province, P. R. China.
Yan
Ying
Y
Li
Ying
Y
Wang
Shuyu
S
Zhang
ZhenZhong
Z
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006207:Half-Life; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry; D008168:Lung / Q000378:metabolism; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014465:Ultrasonics
D000964:Antimetabolites, Antineoplastic; D008055:Lipids; D005472:Fluorouracil