Institute of Chemistry and Biochemistry , Freie Universität Berlin , Takustr. 3 , 14195 Berlin , Germany.
Institute of Laboratory Medicine, Clinical Chemistry, and Pathobiochemistry , Charité-Universitätsmedizin Berlin , Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, CVK Augustenburger Platz 1 , 13353 Berlin , Germany.
Biomacromolecules. 2018 Dec 10;19(12):4524-4533. doi: 10.1021/acs.biomac.8b01100. Epub 2018 Nov 26.
Inflammatory processes are beneficial responses to overcome injury or illness. Knowledge of the underlying mechanisms allows for a specific treatment. Thus, synthetic systems can be generated for a targeted interaction. In this context, dendritic polyglycerol sulfates (dPGS) have been investigated as anti-inflammatory compounds. Biodegradable systems are required to prevent compound accumulation in the body. Here we present biodegradable analogs of dPGS based on hyperbranched poly(glycidol- co-caprolactone) bearing a hydrophilic sulfate outer shell (hPG- co-PCLS). The copolymers were investigated regarding their physical and chemical properties. The cytocompatibility was confirmed using A549, Caco-2, and HaCaT cells. Internalization of hPG- co-PCLS by A549 and Caco-2 cells was observed as well. Moreover, we demonstrated that hPG- co-PCLS acted as a competitive inhibitor of the leukocytic cell adhesion receptor L-selectin. Further, a reduction of complement activity was observed. These new biodegradable dPGS analogs are therefore attractive for therapeutic applications regarding inflammatory diseases.
炎症过程是克服损伤或疾病的有益反应。对潜在机制的了解可实现特定的治疗。因此,可以生成用于靶向相互作用的合成系统。在这种情况下,已研究了树枝状多聚甘油硫酸盐(dPGS)作为抗炎化合物。需要可生物降解的系统来防止化合物在体内积累。在这里,我们提出了基于具有亲水性硫酸盐外壳的超支化聚(环氧甘油-共-己内酯)的 dPGS 的可生物降解类似物(hPG-共-PCLS)。研究了共聚物的物理和化学性质。使用 A549、Caco-2 和 HaCaT 细胞证实了细胞相容性。还观察到 hPG-共-PCLS 被 A549 和 Caco-2 细胞内化。此外,我们证明 hPG-共-PCLS 作为白细胞细胞黏附受体 L-选择素的竞争性抑制剂起作用。此外,还观察到补体活性降低。因此,这些新的可生物降解的 dPGS 类似物在炎症性疾病的治疗应用中很有吸引力。