Preparation of floxuridine diacetate solid lipid nanoparticles

    LIAN Jiaª²Fang£¬ZHANG Sanª²Qi£¬GU Yi£¬SHI Xiaoª²Peng£¬XI Miaoª²Miao

    1Department of Pharmacy£¬Xijing Hospital£¬Xi¬ðan 710033, China, 2Bethune Military Medical College, Shijiazhuang 050081, China, Fourth Military Medical University

    ¡¾Abstract¡¿ AIM: To prepare floxuridine diacetate solid lipid nanoparticles (FUDRAª²SLN) so as to improve the treatment efficacy and reduce the side effects of floxuridine (FUDR). METHODS: FUDR was esterified with acetic anhydride in the presence of pyridine and 4ª²dimethylaminopyridine. The structure of expected compound, floxuridine diacetate (FUDRA)£¬was identified by proton nuclear magnetic resonance. The stability of FUDRA in mouse serum and tissue homogenates and octanolª²buffer partition coeffient of FUDRA were investigated by reversed phase high performance liquid chromatography (RPª²HPLC). FUDRA was used to prepare FUDRAª²SLN by dry membrane technique. Transmission electron microscopy was employed to study the shape and particle diameter distribution of FUDRAª²SLN. Drug loading and entrapment efficiency were also determined by RPª²HPLC. RESULTS: FUDRA was more stable in weak acid solution than in base solution, hydrolyzed fast in serum and tissue homogenates, especially in liver homogenate. The partition coefficient of FUDRA was 58.13. The diameter distribution of FUDRAª²SLN was (208¡À53) nm, drug loading was 7.63% and entrapment efficiency was 94.21%. CONCLUSION: The lipophilicity of FUDR is dramatically increased after esterification with acetic anhydride. FUDRAª²SLN has a high entrapment efficiency and a good distribution in size. ......