Inhibition of bacterial growth and intramniotic infection in a guinea pig model of chorioamnionitis using PAMAM dendrimers

Bing Wang, Raghavendra S. Navath, Anupa R. Menjoge, Bindu Balakrishnan, Robert Bellair, Hui Dai, Roberto Romero, Sujatha Kannan, Rangaramanujam M. Kannan

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


Dendrimers have emerged as topical microbicides to treat vaginal infections. This study explores the in vitro, in vivo antimicrobial activity of PAMAM dendrimers, and the associated mechanism. Interestingly, topical cervical application of 500μg of generation-4 neutral dendrimer (G4-PAMAM-OH) showed potential to treat the Escherichia coli induced ascending uterine infection in guinea pig model of chorioamnionitis. Amniotic fluid collected from different gestational sacs of infected guinea pigs posttreatment showed absence of E. coli growth in the cultures plated with it. The cytokine level [tumor necrosis factor (TNFα) and interleukin (IL-6 and IL-1β)] in placenta of the G4-PAMAM-OH treated animals were comparable to those in healthy animals while these were notably high in infected animals. Since, antibacterial activity of amine-terminated PAMAM dendrimers is known, the activity of hydroxyl and carboxylic acid terminated PAMAM dendrimers was compared with it. Though the G4-PAMAM-NH2 shows superior antibacterial activity, it was found to be cytotoxic to human cervical epithelial cell line above 10μg/mL, while the G4-PAMAM-OH was non-cytotoxic up to 1mg/mL concentration. Cell integrity, outer (OM) and inner (IM) membrane permeabilization assays showed that G4-PAMAM-OH dendrimer efficiently changed the OM permeability, while G4-PAMAM-NH2 and G3.5-PAMAM-COOH damaged both OM and IM causing the bacterial lysis. The possible antibacterial mechanism are G4-PAMAM-NH2 acts as polycation binding to the polyanionic lipopolysaccharide in E. coli, the G4-PAMAM-OH forms hydrogen bonds with the hydrophilic O-antigens in E. coli membrane and the G3.5-PAMAM-COOH acts as a polyanion, chelating the divalent ions in outer cell membrane of E. coli. This is the first study which shows that G4-PAMAM-OH dendrimer acts as an antibacterial agent.

Original languageEnglish (US)
Pages (from-to)298-308
Number of pages11
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - Aug 2010
Externally publishedYes


  • Antimicrobial activity
  • Cell membrane
  • Cytotoxicity
  • Gram negative bacteria
  • PAMAM dendrimer

ASJC Scopus subject areas

  • Pharmaceutical Science


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