Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Enhanced Liver Targeting by Synthesis of $N_{\b{1}}-Stearyl-5-Fu$ and Incorporation into Solid lipid Nanoparticles

  • Yu, Bo-Tao (West China School of Pharmacy, Sichuan University) ;
  • Xun-Sun (West China School of Pharmacy, Sichuan University) ;
  • Zhang, Zhi-Rong (West China School of Pharmacy, Sichuan University)
  • Published : 2003.11.01
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Abstract

To enhance the liver targeting and reduce the side effects of 5-fluorouracil (5-Fu), it was acylated by stearyl chloride to obtain .$\b{N}_{\b{1}}$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: $V_d$=0.04336L/kg, $T_{1/2} \beta$=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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References

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