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KMID : 0043320030260121096
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Archives of Pharmacal Research
2003 Volume.26 No. 12 p.1096 ~ p.1101
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Enhanced Liver Targeting by Synthesis of N1-stearyl-5-Fu and Incorporation into Solid lipid Nanoparticles
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Yu Bo-Tao
Xun-Sun
Zhang Zhi-rong
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Abstract
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To enhance the liver targeting and reduce the side effects of 5-fluorouracil (5-Fu), it was acylated by stearyl chloride to obtain .stearyl-5-Fu (5-FuS). The chemical structure of the prodrug was confirmed by Nuclear Magnetic Resonance and Infrared Spectrometry. 5-FuS was incorporated into solid lipid nanoparticles (SLN), which were prepared by the physical agglomeration method. The mean diameter of 5-FuS-SLN was 240.19 nm and the drug loading was 20.53%. The release characteristics in vitro of 5-FuS-SLN were fitted to the first-order pharmacokinetic model. Compared with 5-Fu injection, a study on the distribution of 5-FuS-SLN in mice showed that 5-FuS-SLN could double 5-Fu concentration in mice livers. The main pharmacokinetic parameters of 5-FuS-SLN in rabbits is shown as follows: =0.04336L/kg, =1.2834h, CL=0.1632 L/h. In conclusion, 5-FuS-SLN has significant liver targeting properties. The employment of a prodrug to enhance drug liposoluble properties and the preparation method presented in this paper, seem to be an alternative strategy to the traditional colloidal delivery system.
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KEYWORD
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5-Fluorouracil (5-Fu), Prodrug, Solid lipid nanoparticles (SLN), Targeted drug delivery system
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