甲氨蝶呤插层MgAl-LDH复合物的制备与释药性能

Preparation and Release Properties of Methotrexate Intercalated MgAl-LDH Composites

摘要:

以Mg(NO3)2•6H2O和Al(NO3)3•9H2O为主要原料，采用共沉淀联合水热合成法制备了甲氨蝶呤插层镁铝层状双氢氧化物复合物（MTX-LDH），通过正交实验分析了主要工艺条件对MTX-LDH复合物载药率、粒径及其分散性的影响。结果表明：当反应温度为60 ℃，Mg(NO3)2•6H2O和Al(NO3)3•9H2O的投入量分别为2.67 mmol和1.33 mmol，MTX和聚乙二醇400加入量分别为0.2 mmol和15 mL时，复合产物单分散性良好，粒径均值为175.6 nm，载药率达18.9%。利用FTIR、XRD、TG以及TEM等表征手段，对样品结构、热力学性质和微观形貌进行了研究。重点考察了MTX-LDH复合物在不同pH缓冲溶液中的释药性能，表明其具备pH响应型释放特性，在pH=5.8的弱酸环境中缓释效果良好，12 h累积释药率为93.7%，并通过热力学释药模型确定其缓释机理为层板溶蚀与置换扩散并存的缓释机制。

Abstract:

Methotrexate intercalated Mg-Al layered double hydroxide composites (MTX-LDH) were prepared via combination of coprecipitation and hydrothermal synthesis by using Mg(NO3)2•6H2O and Al(NO3)3•9H2O as main materials. The effects of main technological conditions on drug loading rate, particle size and dispersion of MTX-LDH composite were analyzed by orthogonal test. The results showed that the composites had good monodispersity, suitable particle size (175.6nm), and high drug loading rate (18.9%) when the reaction temperature was 60℃, and the amount of Mg(NO3)2•6H2O, Al(NO3)3•9H2O, MTX and polyethylene glycol 400 were 2.67 mmol, 1.33 mmol, 0.2 mmol and 15 mL respectively. The structure, thermodynamic properties and micro-morphology of the samples were studied by FTIR, XRD, TG and TEM. The release properties of MTX-LDH composite particles in different pH buffer solutions were investigated emphatically. It was indicated that the composites had the characteristics of pH-responsive release and good sustained release properties in weak acid environment with pH=5.8, and the cumulative release rate at 12 h was up to 93.7%. Moreover, the release mechanism of laminate dissolution coexist with displacement diffusion was confirmed by the thermodynamic release model.