Chung J T, Vlugt-Wensink K D F, Hennink W E, Zhang Z
Centre for Formulation Engineering, Chemical Engineering, School of Engineering, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Int J Pharm. 2005 Jan 6;288(1):51-61. doi: 10.1016/j.ijpharm.2004.09.011. Epub 2004 Nov 6.
Dextran-hydroxy-ethyl-methacrylate (dex-HEMA) hydrogels in the form of microspheres are an attractive system for the controlled delivery of protein drugs. In this work, the microspheres were prepared by a water-in-water emulsion polymerization process. The polymerization reaction was initiated by potassium peroxodisulfate (KPS) and catalyzed by N,N,N',N'-tetramethylethylenediamine (TEMED). The effect of the initiator concentration, reaction temperature and pH on the mechanical and network properties of the microspheres were investigated. The size and size distribution of the microspheres, equilibrium water content, and methacrylate conversion were also determined. The mechanical properties of single microspheres were measured by a micromanipulation technique and the rheological characteristics of the same material in the form of macroscopic hydrogel slabs were determined by a controlled stress rheometer. The results showed that the Young's moduli of the microspheres and of macroscopic slabs measured by these two methods were in good agreement. Higher KPS initiator concentrations resulted in a more rapid polymerization with a shorter gelation and lag time, and a higher Young's modulus of the gels. An increase in temperature also resulted in a more rapid polymerization with a shorter gelation and lag time. However, the Young's modulus of the gels decreased with an increase in polymerization temperature. The pH had no significant effect on the mechanical properties of the microspheres. This study demonstrates that the network properties of dex-HEMA hydrogels can be tailored by the polymerization conditions, which opens the possibility to modulate the release rate of entrapped compounds.
微球状的葡聚糖 - 甲基丙烯酸羟乙酯(dex - HEMA)水凝胶是用于蛋白质药物控释的一种有吸引力的体系。在这项工作中,微球通过水包水乳液聚合工艺制备。聚合反应由过硫酸钾(KPS)引发,并由N,N,N',N' - 四甲基乙二胺(TEMED)催化。研究了引发剂浓度、反应温度和pH对微球力学和网络性能的影响。还测定了微球的尺寸和尺寸分布、平衡含水量以及甲基丙烯酸酯转化率。通过微操纵技术测量单个微球的力学性能,并通过控制应力流变仪测定宏观水凝胶板形式的相同材料的流变特性。结果表明,通过这两种方法测量的微球和宏观板的杨氏模量吻合良好。较高的KPS引发剂浓度导致聚合更快,凝胶化和滞后时间更短,凝胶的杨氏模量更高。温度升高也导致聚合更快,凝胶化和滞后时间更短。然而,凝胶的杨氏模量随着聚合温度的升高而降低。pH对微球的力学性能没有显著影响。这项研究表明,dex - HEMA水凝胶的网络性能可以通过聚合条件进行调整,这为调节包封化合物的释放速率提供了可能性。