Stillman Zachary S, Jarai Bader M, Raman Nisha, Patel Premal, Fromen Catherine A
Department of Chemical and Biomolecular Engineering, University of Delaware.
Polym Chem. 2020 Jan 14;11(2):568-580. doi: 10.1039/c9py01206k. Epub 2019 Oct 23.
Hydrogel nanoparticles (also known as nanogels) have been utilized for a wide range of applications including analytics, sensors, drug delivery, immune engineering, and biotechnology. While these types of nanoparticles can be characterized using standard colloidal characterization techniques, degradation profiles typically must be inferred from those of bulk gels with the same formulation, typically by applying swelling ratios and rheological measurements that tend to severely underestimate nanoparticle degradation rates. Herein, we present an analysis of the degradation via ester hydrolysis of poly(ethylene glycol) diacrylate (PEGDA)-based hydrogel nanoparticles in water, varied pH conditions, and redox environments. We perform this characterization using thermogravimetric analysis and mass spectrometry to analyze rates of degradation and products released, respectively, and compare results to those for equivalent bulk gel formulations. Our findings show that PEGDA-based nanoparticles display significant mass loss over time accompanied by negligible changes in hydrodynamic diameter, indicating a bulk mode of degradation. Nanoparticle mass loss occurs at a much higher rate than for bulk gels under comparable incubation conditions, confirming that bulk gel degradation serves as a poor surrogate for nanoparticle degradation. We further demonstrate that the incorporation of other diacrylate-based co-monomers drastically accelerates nanoparticle degradation rates. Through formulation considerations of co-monomer content and weight percent of PEGDA, we demonstrate the ability to tune the degradation rates of PEGDA-based nanoparticles on a range of hours to weeks. These findings highlight critical design considerations for enhancing the tunability and utility of PEGDA hydrogel nanoparticles and introduce a rigorous framework for the characterization of nanogel degradation.
水凝胶纳米颗粒（也称为纳米凝胶）已被广泛应用于分析、传感器、药物递送、免疫工程和生物技术等领域。虽然这类纳米颗粒可以使用标准的胶体表征技术进行表征，但降解曲线通常必须从具有相同配方的块状凝胶的降解曲线推断得出，通常是通过应用溶胀率和流变学测量方法，而这些方法往往会严重低估纳米颗粒的降解速率。在此，我们对基于聚乙二醇二丙烯酸酯（PEGDA）的水凝胶纳米颗粒在水、不同pH条件和氧化还原环境中的酯水解降解进行了分析。我们分别使用热重分析和质谱进行表征，以分析降解速率和释放的产物，并将结果与等效块状凝胶配方的结果进行比较。我们的研究结果表明，基于PEGDA的纳米颗粒随着时间的推移会出现显著的质量损失，而流体动力学直径的变化可以忽略不计，这表明是一种整体降解模式。在可比的孵育条件下，纳米颗粒的质量损失速率比块状凝胶高得多，这证实了块状凝胶降解不能很好地代表纳米颗粒降解。我们进一步证明了加入其他基于二丙烯酸酯的共聚单体可显著加速纳米颗粒的降解速率。通过考虑共聚单体含量和PEGDA的重量百分比的配方，我们展示了在数小时到数周的范围内调节基于PEGDA的纳米颗粒降解速率的能力。这些发现突出了增强PEGDA水凝胶纳米颗粒的可调性和实用性的关键设计考虑因素，并引入了一个严格的纳米凝胶降解表征框架。
