Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan 48202, USA.
Nanomedicine. 2011 Dec;7(6):935-44. doi: 10.1016/j.nano.2011.04.008. Epub 2011 May 19.
Chlamydia trachomatis is an important bacterial pathogen known to be etiological in genital infections, as well as several serious disease sequelae, including inflammatory arthritis. Chlamydiae can persist in infection, making treatment with antibiotics such as azithromycin (AZ) a challenge. The authors explore the use of neutral generation-4 polyamidoamine (PAMAM) dendrimers as intracellular drug-delivery vehicles into chlamydial inclusions. Azithromycin was successfully conjugated with the dendrimers, and the conjugate (D-AZ) released ≈ 90% of the drug over 16 hours. The conjugate readily entered both the Chlamydia-infected HEp-2 cells and the chlamydial inclusions. The conjugate was significantly better than free drug in preventing productive infections in the cells when added at the time of infection, and better in reducing the size and number of inclusions when added either 24 hours or 48 hours post infection. These studies show that dendrimers can deliver drugs efficiently to growing intracellular C. trachomatis, even if the organism is in the persistent form.
In this report, the use of polyamidoamine dendrimers as intracellular drug-delivery vehicles into chlamydial inclusions is investigated. This method results in efficient intracellular delivery of azithromycin to address chlamydia infection.
沙眼衣原体是一种重要的细菌病原体，已知其与生殖器感染以及几种严重的疾病后遗症有关，包括炎症性关节炎。衣原体可以在感染中持续存在，这使得使用抗生素如阿奇霉素（AZ）进行治疗成为一个挑战。作者探索了使用第四代聚酰胺-胺（PAMAM）树枝状聚合物作为细胞内药物输送载体进入衣原体包涵体。阿奇霉素成功地与树枝状聚合物缀合，缀合物（D-AZ）在 16 小时内释放了约 90%的药物。该缀合物很容易进入感染的 HEp-2 细胞和衣原体包涵体。与感染时添加的游离药物相比，该缀合物在预防细胞中的产感染方面明显更好，并且在感染后 24 小时或 48 小时添加时，更好地减少了包涵体的大小和数量。这些研究表明，树枝状聚合物可以有效地将药物递送到生长中的细胞内沙眼衣原体，即使该生物体处于持续形式。
本报告研究了聚酰胺-胺树枝状聚合物作为细胞内药物输送载体进入衣原体包涵体的用途。该方法可有效将阿奇霉素递送至细胞内，以解决衣原体感染问题。
