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Enhanced liver targeting by synthesis ofN 1-stearyl-5-Fu and incorporation into solid lipid nanoparticles

Abstract

To enhance the liver targeting and reduce the side effects of5-fluorouracil (5-Fu), it was acylated by stearyl chloride to obtain N1stearyl-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 characteristicsin 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: Vd=0.04336L/kg, T1/2 β=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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Correspondence to Bo-Tao Yu or Xun Sun or Zhi-Rong Zhang.

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Yu, B., Sun, X. & Zhang, Z. Enhanced liver targeting by synthesis ofN 1-stearyl-5-Fu and incorporation into solid lipid nanoparticles. Arch Pharm Res 26, 1096–1101 (2003). https://doi.org/10.1007/BF02994764

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Key words

  • 5-Fluorouracil (5-Fu)
  • Prodrug
  • Solid lipid nanoparticles (SLN)
  • Targeted drug delivery system