Morrison Nolan, Vogel Brandon M
Department of Chemical Engineering, Bucknell University, Lewisburg, PA 17837, USA.
Gels. 2023 Nov 20;9(11):917. doi: 10.3390/gels9110917.
Injectable, localized drug delivery using hydrogels made from ethoxylated trimethylolpropane tri-3-mercaptopropionate (ETTMP) and poly(ethylene glycol) diacrylate (PEGDA) has shown great potential due to these hydrogels' ability to exhibit non-swelling behavior and tunable drug release properties. However, current synthesis methods in the literature suffer from poor ETTMP solubility in water, slow gelation times exceeding 20 min, and a lack of reproducibility. To address these limitations, we have developed a reliable synthesis procedure and conducted a sensitivity analysis of key variables. This has enabled us to synthesize ETTMP-PEGDA hydrogels in a polymer concentration range of 15 to 90 wt% with gelation times of less than 2 min and moduli ranging from 3.5 to 190 kPa. We overcame two synthesis limitations by identifying the impact of residual mercaptopropionic acid and alumina purification column height on gelation time and by premixing ETTMP and PEGDA to overcome low ETTMP solubility in water. Our ETTMP-PEGDA mixture can be stored at -20 °C for up to 2 months without crosslinking, allowing easy storage and shipment. These and previous results demonstrate the potential of ETTMP-PEGDA hydrogels as promising candidates for injectable, localized drug delivery with tunable drug release properties.
使用由乙氧基化三羟甲基丙烷三 - 3 - 巯基丙酸酯（ETTMP）和聚乙二醇二丙烯酸酯（PEGDA）制成的水凝胶进行可注射的局部药物递送，由于这些水凝胶具有非溶胀行为和可调的药物释放特性，已显示出巨大潜力。然而，文献中目前的合成方法存在ETTMP在水中溶解度差、凝胶化时间超过20分钟且缺乏可重复性等问题。为了解决这些局限性，我们开发了一种可靠的合成程序，并对关键变量进行了敏感性分析。这使我们能够在聚合物浓度范围为15至90 wt%的情况下合成ETTMP - PEGDA水凝胶，凝胶化时间小于2分钟，模量范围为3.5至190 kPa。我们通过确定残留巯基丙酸和氧化铝纯化柱高度对凝胶化时间的影响，以及通过预混合ETTMP和PEGDA来克服ETTMP在水中的低溶解度，克服了两个合成限制。我们的ETTMP - PEGDA混合物可以在 - 20°C下储存长达2个月而不发生交联，便于储存和运输。这些以及先前的结果证明了ETTMP - PEGDA水凝胶作为具有可调药物释放特性的可注射局部药物递送的有前途候选物的潜力。
