Hydrogel‐based drug depot formulations are of great interest for therapeutic applications. While the biological activity of such drug depots is often characterized well, the influence of incorporated drug or drug‐loaded micelles on the gelation properties of the hydrogel matrix is less investigated. However, the latter is of great importance from fundamental and application points of view as it informs on the physicochemical interactions of drugs and water‐swollen polymer networks and it determines injectability, depot stability, as well as drug‐release kinetics. Here, the impact of incorporated drug, neat polymer micelles, and drug‐loaded micelles on the viscoelastic properties of a cytocompatible hydrogel is investigated systematically. To challenge the hydrogel with regard to the desired application as injectable drug depot, curcumin (CUR) is chosen as a model compound due to its very low‐water solubility and limited stability. CUR is either directly solubilized by the hydrogel or pre‐incorporated into polymer micelles. Interference of CUR with the temperature‐induced gelation process can be suppressed by pre‐incorporation into polymer micelles forming a binary drug delivery system. Drug release from a collagen matrix is studied in a trans‐well setup. Compared to direct injection of drug formulations, the hydrogel‐based systems show improved and extended drug release over 10 weeks.

中文翻译：

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将超高载药量胶束和可注射水凝胶药库相结合，以延长药物释放时间

基于水凝胶的药物仓库配方对于治疗应用非常感兴趣。尽管通常可以很好地表征此类药物仓库的生物活性，但很少研究掺入的药物或载有胶束的胶束对水凝胶基质胶凝特性的影响。但是，从基础和应用的角度来看，后者非常重要，因为它可以了解药物与水溶胀的聚合物网络的物理化学相互作用，并决定注射剂，储库稳定性以及药物释放动力学。在这里，系统地研究了掺入的药物，纯净聚合物胶束和载药胶束对细胞相容性水凝胶的粘弹性的影响。为了就所需的可注射药物贮存库的应用挑战水凝胶，姜黄素（CUR）因其极低的水溶性和有限的稳定性而被选作模型化合物。CUR可以直接被水凝胶溶解，也可以预先掺入聚合物胶束中。通过将CUR预掺入形成二元药物递送系统的聚合物胶束中，可以抑制CUR对温度诱导的胶凝过程的干扰。胶原蛋白基质中的药物释放是通过跨孔装置进行研究的。与直接注射药物制剂相比，基于水凝胶的系统在10周内显示出改善和延长的药物释放。通过将CUR预掺入形成二元药物递送系统的聚合物胶束中，可以抑制CUR对温度诱导的胶凝过程的干扰。胶原蛋白基质中的药物释放是通过跨孔装置进行研究的。与直接注射药物制剂相比，基于水凝胶的系统在10周内显示出改善和延长的药物释放。通过将CUR预掺入形成二元药物递送系统的聚合物胶束中，可以抑制CUR对温度诱导的胶凝过程的干扰。胶原蛋白基质中的药物释放是通过跨孔装置进行研究的。与直接注射药物制剂相比，基于水凝胶的系统在10周内显示出改善和延长的药物释放。