Technische Universität Braunschweig, Institut für Pharmazeutische Technologie, Mendelssohnstr. 1, 38106 Braunschweig, Germany.
Int J Pharm. 2012 Oct 15;436(1-2):677-84. doi: 10.1016/j.ijpharm.2012.07.021. Epub 2012 Jul 20.
Hydrogels are under investigation as long term delivery systems for biomacromolecules as active pharmaceutical ingredients. The release behavior of hydrogels can be tailored during the fabrication process. This study investigates the applicability of fluxgate magnetorelaxometry (MRX) as a tool to characterize the release properties of such long term drug delivery depots. MRX is based on the use of superparamagnetic core-shell nanoparticles as model substances. The feasibility of using superparamagnetic nanoparticles to study the degradation of and the associated release from hydrogel cylinders and hydrogel microspheres was a major point of interest. Gels prepared from two types of photo crosslinkable polymers based on modified hydroxyethylstarch, specifically hydroxyethyl starch-hydroxyethyl methacrylate (HES-HEMA) and hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)(6)MA), were analyzed. MRX analysis of the incorporated nanoparticles allowed to evaluate the influence of different crosslinking conditions during hydrogel production as well as to follow the increase in nanoparticle mobility as a result of hydrogel degradation during release studies. Conventional release studies with fluorescent markers (half-change method) were performed for comparison. MRX with superparamagnetic nanoparticles as model substances is a promising method to analyze pharmaceutically relevant processes such as the degradation of hydrogel drug carrier systems. In contrast to conventional release experiments MRX allows measurements in closed vials (reducing loss of sample and sampling errors), in opaque media and at low magnetic nanoparticle concentrations. Magnetic markers possess a better long-term stability than fluorescent ones and are thus also promising for the use in in vivo studies.
水凝胶作为生物大分子的长期药物输送系统，作为活性药物成分正在被研究。水凝胶的释放行为可以在制造过程中进行调整。本研究探讨了通量门磁弛豫测量（MRX）作为一种工具来表征这种长期药物输送库的释放特性的适用性。MRX 基于超顺磁核壳纳米粒子作为模型物质的使用。使用超顺磁纳米粒子研究水凝胶圆柱体和水凝胶微球的降解及其相关释放的可行性是一个主要关注点。分析了两种基于改性羟乙基淀粉的光交联聚合物制备的凝胶，具体为羟乙基淀粉-羟乙基甲基丙烯酸酯（HES-HEMA）和羟乙基淀粉-聚乙二醇甲基丙烯酸酯（HES-P（EG）（6）MA）。掺入纳米粒子的 MRX 分析允许评估在水凝胶生产过程中不同交联条件的影响，以及在释放研究中由于水凝胶降解导致纳米粒子迁移率增加。进行了荧光标记物（半变化法）的常规释放研究作为比较。使用超顺磁纳米粒子作为模型物质的 MRX 是分析药物相关过程（如水凝胶药物载体系统的降解）的一种很有前途的方法。与传统的释放实验相比，MRX 允许在封闭小瓶中进行测量（减少样品损失和采样误差）、在不透明介质中和在低磁纳米粒子浓度下进行测量。磁性标记物比荧光标记物具有更好的长期稳定性，因此也有望用于体内研究。
