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

药品的使用对提高生活质量有决定性的贡献，医药行业的营业额也相应较大。生物技术活性成分，如肽和蛋白质，通常比传统的活性成分大，稳定性有限。当口服给药时，它们被蛋白酶降解或被胃的酸性环境分解。因此，治疗性蛋白质通过注射给药，而不是天然的、侵入性较小且较便宜的口服途径。为了确保在未来容易获得使用不太稳定的分子的成功治疗，递送方法也必须沿着生物技术和生物活性分子量的增加而发展。水凝胶将活性成分或其他生物活性材料封装在其三维网络结构中，从而保护它们，为已建立的和文献已知的药物递送变体提供了一种有前途的替代方案。在目标部位，它们随后均匀地释放，或者在自调节药物递送系统（DDS）的情况下，响应于外部刺激如pH在短时间内释放。已经探索了从模拟胃肠道的介质中的水凝胶的pH敏感性释放用于口服递送，并且除了其他缺点之外，机械稳定性太低以及对用于药物的外部刺激的反应太慢。为了克服水凝胶在医学应用中的缺点，本项目旨在研究基于聚合离子液体（PIL）的水凝胶。精确的结肠特异性药物递送要求递送系统中的触发机制仅响应于结肠特异性的生理条件。为了实现这一目标，该项目提出了新的偶氮水凝胶作为剂型，使口服结肠特异性交付。为了在早期阶段预测释放和溶胀曲线，将开发三维多场模型来预测力学行为以及描述药物释放机制。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，用于靶向药物释放到结肠中，2）开发基于连续力学的多场模型，以代表水凝胶响应pH和酶变化的药物释放。

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.