PAMAM dendrimer-azithromycin conjugate nanodevices for the treatment of Chlamydia trachomatis infections.

Abstract

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.