Völlmecke Katharina, Kramer Maurice, Horky Corinna, Dückmann Oliver, Mulac Dennis, Langer Klaus, Kuckling Dirk
Paderborn University Warburger Straße 100 33098 Paderborn Germany
Institute of Pharmaceutical Technology and Biopharmacy, University of Münster Corrensstr. 48 D-48149 Münster Germany.
RSC Adv. 2024 Nov 7;14(48):35568-35577. doi: 10.1039/d4ra07228f. eCollection 2024 Nov 4.
Over the last few decades, nanotechnology has established to be a promising field in medicine. A remaining dominant challenge in today's pharmacotherapy is the limited selectivity of active pharmaceutical ingredients and associated undesirable side effects. Controlled drug release can be promoted by smart drug delivery systems, which release embedded API primarily depending on specific stimuli. Consequently, also the microenvironment of tumor tissue can be used advantageously. Dithiothreitol (DTT) based self-immolative polydisulfides were synthesized that preferentially respond to pathologically increased glutathione (GSH) concentrations, as found in solid tumors. The synthesis with different degrees of polymerisation was investigated as well as the synthesis of a copolymer consisting of dithiothreitol and butanedithiol (BDT). Toxicity tests were carried out on pure polymers and their degradation products. The ability to degrade was examined at pathological and physiological glutathione concentrations in order to test the suitability of the polymer as a matrix for nanoparticulate carrier systems. In addition, the processability of one polymer into nanoparticles was investigated as well as the degradation behaviour with glutathione.
在过去几十年里，纳米技术已成为医学领域一个很有前景的领域。当今药物治疗中一个仍然主要的挑战是活性药物成分的选择性有限以及相关的不良副作用。智能药物递送系统可以促进药物的可控释放，这种系统主要根据特定刺激来释放包埋的活性药物成分。因此，肿瘤组织的微环境也可以得到有效利用。合成了基于二硫苏糖醇（DTT）的自毁型聚二硫化物，其对实体瘤中病理升高的谷胱甘肽（GSH）浓度有优先响应。研究了不同聚合度的合成以及由二硫苏糖醇和丁二硫醇（BDT）组成的共聚物的合成。对纯聚合物及其降解产物进行了毒性测试。在病理和生理谷胱甘肽浓度下检查了降解能力，以测试该聚合物作为纳米颗粒载体系统基质的适用性。此外，还研究了一种聚合物加工成纳米颗粒的可加工性以及其与谷胱甘肽的降解行为。
