title: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan 48202, USA.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Mishra
authors.forename: Kishore
authors.initials: K
authors.lastname: Kotta
authors.forename: Mirabela
authors.initials: M
authors.lastname: Hali
authors.forename: Susan
authors.initials: S
authors.lastname: Wykes
authors.forename: Herve C
authors.initials: HC
authors.lastname: Gerard
authors.forename: Alan P
authors.initials: AP
authors.lastname: Hudson
authors.forename: Judith A
authors.initials: JA
authors.lastname: Whittum-Hudson
authors.forename: Rangaramanujam M
authors.initials: RM
authors.lastname: Kannan
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017963:Azithromycin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability; D002690:Chlamydia Infections / Q000188:drug therapy*; D002692:Chlamydia trachomatis / Q000187:drug effects*; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D017963:Azithromycin