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  • Title: Novel galactosylated SLN for hepatocyte-selective targeting of floxuridinyl diacetate.
    Author: Lian J, Zhang S, Wang J, Fang K, Zhang Y, Hao Y.
    Journal: J Drug Target; 2008 Apr; 16(3):250-6. PubMed ID: 18365887.
    Abstract:
    This paper describes the preparation and liver-targeting traits of new solid lipid nanoparticles (SLN) containing floxuridinyl diacetate (FUDRA) modified with beta-d-galactosides (Gn). FUDRA and Gn were incorporated, respectively, to study the drug loading (DL), drug release, and in vivo distribution property. Transmission electron microscopy analysis revealed that the particle sizes of FUDRA-SLN, FUDRA-G2SLN and FUDRA-G10SLN were 215.3, 91.3 and 106.0 nm, with DLs of 8.20, 8.37 and 8.91%, respectively. In an in vivo study of Specific pathogen-free mice, the complexes were administered via the tail vein. Judging on the basis of 5-fluoro-2'-deoxyuridinum (FUDR) concentration in blood and viscera with HPLC analysis, FUDRA release was confirmed and a significant enrichment of SLN modified with Gn was observed in the liver with Gn complex (targeting rates of SLN-G2 and SLN-G10 are 11.25 and 11.43 for the liver, respectively) in comparison with FUDR-sol (targeting rate is 1.71). In mice, FUDR could be detected in the liver at 40, 160, 320 and 480 min after i.v. administration of FUDR-sol, FUDRA-SLN, FUDRA-G2SLN and FUDRA-G10SLN, respectively. These results suggest that G2 and G10 are ideal materials for preparing active liver targeting SLN. FUDRA-G2SLN and, particularly, FUDRA-G10SLN have desirable hepatocyte-selective targeting and sustained-release action in healthy mice.
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