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Biodegradable Polyglycerol Sulfates Exhibit Promising Features for Anti-inflammatory Applications
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-11-09 00:00:00 , DOI: 10.1021/acs.biomac.8b01100 Magda Ferraro 1 , Kim Silberreis 1, 2 , Ehsan Mohammadifar 1 , Falko Neumann 1 , Jens Dernedde 2 , Rainer Haag 1
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-11-09 00:00:00 , DOI: 10.1021/acs.biomac.8b01100 Magda Ferraro 1 , Kim Silberreis 1, 2 , Ehsan Mohammadifar 1 , Falko Neumann 1 , Jens Dernedde 2 , Rainer Haag 1
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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.
中文翻译：
可生物降解的聚甘油硫酸盐显示出抗炎应用的有前途的功能
炎症过程是克服伤害或疾病的有益反应。对基本机制的知识允许进行特定的处理。因此，可以产生用于目标相互作用的合成系统。在这种情况下，已经研究了树突状聚甘油硫酸盐（dPGS）作为抗炎化合物。需要生物可降解的系统来防止化合物在体内积累。在这里，我们介绍了基于带有亲水性硫酸盐外壳（hPG- co- PCLS）的超支化聚（缩水甘油-co-己内酯）的dPGS的可生物降解类似物。研究了共聚物的物理和化学性质。使用A549，Caco-2和HaCaT细胞确认了细胞相容性。hPG- co的内在化还观察到了由A549和Caco-2细胞引起的-PCLS。此外，我们证明了hPG- co- PCLS可以作为白细胞粘附受体L-选择素的竞争性抑制剂。此外，观察到补体活性降低。因此，这些新的可生物降解的dPGS类似物对于炎症性疾病的治疗应用具有吸引力。
更新日期：2018-11-09
中文翻译：
可生物降解的聚甘油硫酸盐显示出抗炎应用的有前途的功能
炎症过程是克服伤害或疾病的有益反应。对基本机制的知识允许进行特定的处理。因此，可以产生用于目标相互作用的合成系统。在这种情况下，已经研究了树突状聚甘油硫酸盐（dPGS）作为抗炎化合物。需要生物可降解的系统来防止化合物在体内积累。在这里，我们介绍了基于带有亲水性硫酸盐外壳（hPG- co- PCLS）的超支化聚（缩水甘油-co-己内酯）的dPGS的可生物降解类似物。研究了共聚物的物理和化学性质。使用A549，Caco-2和HaCaT细胞确认了细胞相容性。hPG- co的内在化还观察到了由A549和Caco-2细胞引起的-PCLS。此外，我们证明了hPG- co- PCLS可以作为白细胞粘附受体L-选择素的竞争性抑制剂。此外，观察到补体活性降低。因此，这些新的可生物降解的dPGS类似物对于炎症性疾病的治疗应用具有吸引力。
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