Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan 48202, USA.
Nanomedicine. 2011 Jun;7(3):284-94. doi: 10.1016/j.nano.2010.10.008. Epub 2010 Nov 6.
Erythromycin (EM), an antibiotic that has been used for infectious diseases, is now gaining attention because of its novel anti-inflammatory effects. We explore a dendrimer-EM nanodevice for sustained treatment of orthopedic inflammation. To sustain pharmacological activity, EM was conjugated to poly(amidoamine) dendrimer (PAMAM) through an ester bond. A bifunctional PAMAM dendrimer was prepared having neutral hydroxy and reactive amine groups on the surface and was reacted with EM prodrug (EM-2'-glutarate). The cytotoxicity, efficacy and antibacterial properties were evaluated on macrophages (RAW 264.7 cells) associated with periprosthetic inflammation. The conjugate is noncytotoxic and showed significant reduction of nitrite level (by 42% as compared with untreated cells and free EM). The zone of inhibition of the conjugate on bacterial growth at different concentrations showed similar activity compared to free EM. The anti-inflammatory properties of EM combined with the targeting potential of the dendrimer can lead to sustained and targeted intracellular delivery.
In this study, a specific dendrimer-erythromycin conjugate nanodevice is investigated for the treatment of periprosthetic inflammation. The anti-inflammatory properties of erythromycin combined with the targeting potential of the dendrimer can lead to sustained and targeted intracellular delivery.
红霉素（EM）是一种用于治疗传染病的抗生素，由于其具有新颖的抗炎作用，现在受到关注。我们探索了一种树枝状聚合物-EM 纳米装置，用于持续治疗骨科炎症。为了维持药理学活性，通过酯键将 EM 与聚（酰胺-胺）树枝状聚合物（PAMAM）偶联。通过反应性胺基和中性羟基制备了具有双官能团的 PAMAM 树枝状聚合物，并与 EM 前药（EM-2'-戊二酸酯）反应。在与假体周围炎症相关的巨噬细胞（RAW 264.7 细胞）上评估了细胞毒性、功效和抗菌性能。该缀合物无细胞毒性，并显示亚硝酸盐水平显著降低（与未处理的细胞和游离 EM 相比降低了 42%）。在不同浓度下，该缀合物对细菌生长的抑制区与游离 EM 相比具有相似的活性。EM 的抗炎特性与树枝状聚合物的靶向潜力相结合，可以实现持续和靶向的细胞内递药。
在这项研究中，研究了一种特定的树枝状聚合物-红霉素缀合物纳米装置，用于治疗假体周围炎症。红霉素的抗炎特性与树枝状聚合物的靶向潜力相结合，可以实现持续和靶向的细胞内递药。
