Laboratory of Organic and Macromolecular Chemistry (IOMC) , Friedrich Schiller University Jena , Humboldtstraße 10 , 07743 Jena , Germany.
Jena Center for Soft Matter (JCSM) , Friedrich Schiller University Jena , Philosophenweg 7 , 07743 Jena , Germany.
Biomacromolecules. 2019 Jan 14;20(1):130-140. doi: 10.1021/acs.biomac.8b01228. Epub 2018 Nov 8.
The encapsulation of therapeutic compounds into nanosized delivery vectors has become an important strategy to improve efficiency and reduce side effects in drug delivery applications. Here, we report the synthesis of pH-sensitive nanogels, which are based on the monomer N-[(2,2-dimethyl-1,3-dioxolane)methyl]acrylamide (DMDOMA) bearing an acid cleavable acetal group. Degradation studies revealed that these nanogels hydrolyze under acidic conditions and degrade completely, depending on the cross-linker, but are stable in physiological environment. The best performing system was further studied regarding its release kinetics using the anticancer drug doxorubicin. In vitro studies revealed a good compatibility of the unloaded nanogel and the capability of the doxorubicin loaded nanogel to mediate cytotoxic effects in a concentration and time-dependent manner with an even higher efficiency than the free drug. Based on the investigated features, the presented nanogels represent a promising and conveniently prepared alternative to existing carrier systems for drug delivery.
将治疗化合物封装到纳米级的递送载体中已成为提高药物递送应用效率和降低副作用的重要策略。在这里,我们报告了基于带有可酸裂解缩醛基团的单体 N-[(2,2-二甲基-1,3-二氧戊环)甲基]丙烯酰胺 (DMDOMA) 的 pH 敏感纳米凝胶的合成。降解研究表明,这些纳米凝胶在酸性条件下水解,并根据交联剂的不同而完全降解,但在生理环境中稳定。表现最佳的系统进一步研究了其使用抗癌药物阿霉素的释放动力学。体外研究表明,未负载的纳米凝胶具有良好的相容性,负载阿霉素的纳米凝胶能够以浓度和时间依赖的方式介导细胞毒性作用,其效率甚至高于游离药物。基于所研究的特征,所提出的纳米凝胶代表了一种有前途的、方便制备的替代现有药物递送载体系统的选择。