“右旋糖酐-磁性层状复合氢氧化物-氟尿嘧啶”给药系统的超分子组装表征与急毒性水平  

Supra-molecular Assembly Characterization and Urgent Toxic Level of "Dextran-Magnetic Layered Double Hydroxide-Fluorouracil" Drug Delivery System

作　　者：苟国敬[1,2] 王志宇[1] 刘彦红[1,2] 薛冰[1,2] 黄洁[1,2] 孙岳[1,2] 

机构地区：[1]宁夏医科大学医用化学系,银川750004 [2]宁夏医科大学医学科学技术研究中心,银川750004

出　　处：《化学学报》2012年第2期161-169,共9页Acta Chimica Sinica

基　　金：国家自然科学基金(No.20961008);宁夏高等学校科学技术研究重点项目基金(No.200919341);宁夏自然科学基金(No.NZ09102);教育部科学技术研究重点项目基金(No.207127)资助项目~~

摘　　要：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 drug delivery system DMF with a formation of DET-MLDH-FU（dextran-magnetic layered double hydroxide-fluorouracil） was synthesized by the ＂precursor co-precipitation-intercalated assembly with ion exchange-dextran in situ composite-solvent conversion＂ technology,the crystal-phase characteristic and slow-release performance of DMF system were investigated through XRD,IR,TEM,TG characterization and dissolve out experiment in vitro.The urgent toxic levels of DMF and MLDH were inspected through mice animal experiments of irrigation stomach and intraperitoneal injection.The results showed that the XRD of DMF,MLDH-FU and MLDH matched with R-sixtetragonum LDH series,mixed by Fe3.6Fe0.9（O,OH,Cl）9 type crystal-phase and trace iron oxide.The DMF supra-molecular system consisted by DET,MLDH and FU com-ponents had a core-shell structure formed through grading assembly.The drug release model of DMF accorded with the zero-order kinetics equation C-1.162×10-5=4.566×10-7t at pH 7.35 of PBS in vitro,and its rate constant was 4.566×10-7 mol-1？L？m-1.DMF,MLDH-FU and MLDH could be excreted in vivo through nor-mal metabolism,with a tiny oral toxicity.The LD50 of intraperitoneal injection experiment were 2542.8 mg？ kg-1 and 1951.0 mg？kg-1 respectively for DMF and MLDH-FU,which meant all belonged to low toxic sub-stances.Composite assembly with DET produced the antioxidant protection function for the layered structure of MLDH-FU,resulting in selection,separation and encapsulation of different particles,and gave rise to im-proving for the slow-release effect of MLDH-FU,strengthening of controlled-release characteristic for MLDH,and reducing of the urgent toxic levels for DMF drug delivery system.

关 键 词：右旋糖酐-磁性层状复合氢氧化物-氟尿嘧啶给药系统 三级超分子组装 药物释放模型 急毒性水平 

分 类 号：R96[医药卫生—药理学]