基于湿法球磨改性蒙脱土构建可负载疏水药物的海藻酸盐/有机蒙脱土复合凝胶微球及其释药性

Construction of Alginate/Organic Montmorillonite Composite Hydrogel Beads Capable of Loading Hydrophobic Drugs Based on Wet-ball Milling Method Modified Montmorillonite and Their Release Properties

为了构建良好的有机疏水药物载体,以非离子表面活性剂壬基酚聚氧乙烯醚(Np-10)作为改性剂,采用湿法球磨的方法对蒙脱土(MMT)的强极性和结构进行修饰,以提高其与疏水有机药物分子的亲和力。进而以海藻酸盐作为包覆材料,在钙离子的外源交联作用下构建了具有缓控释性能的海藻酸盐/有机蒙脱土复合凝胶微球(SA/OMMT HB)。通过FTIR、XRD、比表面积及孔径分析仪、药物吸附实验、TGA和SEM对所制备的有机蒙脱土(OMMT)和SA/OMMT HB的结构、性能和形貌进行了表征,考察了SA/OMMT HB对疏水性抗炎药物布洛芬的控制释放性能。结果表明,在湿法球磨机械作用下,Np-10成功地插入钠基蒙脱土(Na-MMT)的片层间。改性后OMMT的比表面积由67.69 m^2/g增长至208.31 m^2/g。Na-MMT和OMMT对布洛芬的吸附等温线模型拟合结果表明,OMMT对疏水性药物的亲和力优于Na-MMT,更利于布洛芬的负载。在SA/OMMT HB中,OMMT片层与海藻酸盐以氢键的作用相互结合,该结合方式有助于提高SA/OMMT HB的热稳定性能。同时,OMMT与疏水药物分子良好的亲和力使SA/OMMT HB表现出较好的控释性能。通过Peppas模型方程拟合可知,SA/OMMT HB对布洛芬的释放过程属于Non-Fickian扩散机制,说明药物的自身扩散和复合凝胶微球的溶胀降解共同控制药物的释放速率。

In order to construct a good organic hydrophobic drug carrier,the strong polarity and structural properties of montmorillonite were modified by wet ball-milling method using the nonionic surfactant,nonylphenolethoxylate(Np-10),as the modifier,to improve the montmorillonite’s affinity for hydrophobic organic drug.Furthermore,the alginate/organic montmorillonite composite hydrogel bead(SA/OMMT HB)with slow and controlled release properties was prepared by the use of alginate as the coating material,under the exogenous cross-linking of calcium ions.The structure,properties and morphology of the prepared OMMT and SA/OMMT HB were characterized by FTIR,XRD,specific surface area and pore size analyzer,drug adsorption experiments,TGA and SEM.And the controlled release performance of the hydrophobic anti-inflammatory drug,ibuprofen,from SA/OMMT HB were also investigated.The experimental results showed that Np-10 was successfully inserted into the interlayer of Na-MMT under the action of wet ball-milling.The specific surface area of the modified OMMT increased from 67.69 m^2/g to 208.31 m^2/g.The results of the adsorption isotherm model fitting of ibuprofen by Na-MMT and OMMT showed that the affinity of OMMT for hydrophobic drugs was better than that of Na-MMT,which was more conductive to the loading of ibuprofen.In SA/OMMT HB,the OMMT sheet and alginate were combined by hydrogen bonding,which helped to improve the thermal stability of SA/OMMT HB.Moreover,the good affinity of OMMT to hydrophobic drug allowed SA/OMMT HB to exhibit good controlled release properties.According to the Peppas model equation fitting,the release process of ibuprofen from SA/OMMT HB belonged to the Non-Fickian diffusion mechanism,indicating that the drug itself diffuses and the swelling and degradation of the composite hydrogel beads jointly controlled the release rate of the drug.