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用“前体共沉淀-离子交换插层-原位复合-溶剂转换”技术合成“右旋糖酐-磁性层状复合氢氧化物-氟尿嘧啶”(DET-MLDH-FU,DMF)运载系统,通过XRD,IR,TEM,TG表征及体外释放实验研究了DMF的物相特征与缓释性能,通过对小鼠灌胃和腹腔注射给药考察了DMF与载体MLDH的急毒性水平.结果表明,DMF等超分子的XRD与R-六方LDH衍射特征相符,是Fe3.6Fe0.9(O,OH,Cl)9型LDH及微量Fe3O4的复合晶相,DMF具有DET,MLDH与FU分级组装形成的核壳式构造.体外pH 7.35 PBS溶出介质中,DMF的药物释放遵守零级模型C-1.162×10-5=4.566×10-7t,速率常数4.566×10-7 mol-1?L?m-1.DMF,MLDH-FU及MLDH可经正常代谢排出体外,口服毒性小;腹腔注射DMF的LD50为2542.8 mg?kg-1,MLDH的LD50为1951.0 mg?kg-1,均属低毒性物质.DET的复合组装对Fe(II,III)LDH构架有抗氧化保护作用,对不同MLDH-FU粒子进行选择、分离与包封,提高MLDH-FU的缓释效果、强化MLDH的控释性能,降低给药系统DMF的急毒性水平.
The DET-MLDH-FU (DMF) delivery system was synthesized using the technique of “coprecipitation-ion exchange intercalation-in situ complex-solvent conversion” The phase character and sustained-release performance of DMF were studied by XRD, IR, TEM, TG and in vitro release experiments. The acute toxicity level of DMF and carrier MLDH were investigated by intragastric and intraperitoneal injection. DMF and other supramolecular XRD and R-hexagonal LDH diffraction characteristics, is Fe3.6Fe0.9 (O, OH, Cl) 9 LDH and trace Fe3O4 composite crystal phase, DMF with DET, MLDH and FU grading assembled Core-shell structure in vitro pH 7.35 PBS dissolution medium, DMF drug release comply with the zero-order model C-1.162 × 10-5 = 4.566 × 10-7t, the rate constant of 4.566 × 10-7 mol-1? L? M- 1.DMF, MLDH-FU and MLDH can be excreted through normal metabolism, oral toxicity is small; LD50 of intraperitoneal injection of DMF is 2542.8 mg? Kg-1, LD50 of MLDH is 1951.0 mg? Kg-1, are low toxicity substances. The composite assembly of DET can protect the Fe (II, III) LDH framework against oxidative stress and improve the sustained-release effect of MLDH-FU by selecting, separating and encapsulating different MLDH-FU particles, Acute drug toxicity level system of DMF.