Development of new azo-hydrogels and a numerical multi-field model for colon-specific drug release

用药对提高生活质量具有决定性贡献，医药行业营业额相应较大。生物技术活性成分，如多肽和蛋白质，往往比传统活性成分大，稳定性有限。当口服时，它们会被蛋白酶降解或被胃的酸性环境分解。因此，治疗性蛋白质是通过注射给药的，而不是自然的、侵入性更小、成本更低的口服途径。为了确保在未来用不太稳定的分子进行成功的治疗很容易，给药方法也必须随着生物技术和生物活性分子数量的增加而发展。水凝胶将活性成分或其他生物活性物质包裹在其三维网络结构中，从而保护它们，为现有的和文献所知的药物递送变体提供了一种有前途的替代方案。在靶部位，它们随后被均匀释放，或者在自我调节药物输送系统(DDS)的情况下，在短时间内对外部刺激(如pH)做出反应。水凝胶在模拟胃肠道的介质中对pH敏感的释放已被探索用于口服给药，但除其他缺点外，机械稳定性太低，对外部刺激的反应太慢，不能用于药物治疗。为了克服水凝胶在医学应用中的不足，本项目旨在研究基于聚合离子液体(PILS)的水凝胶。精确的结肠定位给药要求给药系统中的触发机制只对特定于结肠的生理条件做出反应。为了实现这一点，该项目提出了新型偶氮水凝胶作为剂型，使口服结肠定位给药。为了早期预测药物的释放和溶胀情况，将建立一个三维多场模型来预测药物的力学行为和描述药物的释放机理。因此，该项目结合了两个同等重要的中心研究目标：1)一系列新型偶氮水凝胶的合成和表征，用于定向药物释放到结肠中；2)发展基于连续介质力学的多场模型，以表示药物从水凝胶中释放对pH和酶的响应。

The use of drugs makes a decisive contribution to improving the quality of life, and the turnover of the pharmaceutical industry is correspondingly large. Biotechnological active ingredients, such as peptides and proteins, are often larger than traditional active ingredients and have limited stability. When administered orally, they are degraded by proteases or decomposed by the acidic environment of the stomach. Therefore, therapeutic proteins are administered via injections, rather than the natural, less invasive and less expensive oral route. To ensure that successful therapy with less stable molecules is easily accessible in the future, the delivery methods must also develop along with increasing amount of biotechnological and bioactive molecules. Hydrogels, which encapsulate active ingredients or other bioactive materials in their three-dimensional network structure and thus protect them, offer a promising alternative to established and literature-known variants of drug delivery. At the target site, they are subsequently released uniformly or, in the case of self-regulating drug delivery systems (DDS), within a short time in response to external stimuli such as pH. The pH-sensitive release from hydrogels in media that simulate the gastrointestinal tract has been explored for oral delivery and show, among other drawbacks, too low mechanical stability and too slow response to external stimuli for use in medication. To overcome the disadvantages of hydrogels in medical applications, the present project aims to investigate hydrogels based on polymerized ionic liquids (PILs). Precise colon-specific drug delivery requires that the trigger mechanism in the delivery system responds only to physiological conditions specific to the colon. To achieve this, this project proposes novel azo-hydrogels as dosage forms that enable oral colon-specific delivery. In order to predict the release and swelling profile at an early stage, a three-dimensional multi-field model will be developed to predict the mechanical behavior as well as to describe the mechanisms of drug release. The project thus combines two central research aims of equal importance: 1) The synthesis and characterization of a series of novel azo-hydrogels for targeted drug release into the colon, 2) The development of a continuum mechanics-based multi-field model to represent drug release from hydrogels in response to pH and enzyme changes.