Fetal uptake of intra-amniotically delivered dendrimers in a mouse model of intrauterine inflammation and preterm birth

Irina Burd, Fan Zhang, Tahani Dada, Manoj K. Mishra, Talaibek Borbiev, Wojciech G. Lesniak, Haitham Baghlaf, Sujatha Kannan, Rangaramanujam M. Kannan

Research output: Contribution to journalArticle

Abstract

Intrauterine inflammation is associated with preterm birth and can lead to fetal neuroinflammation and neurobehavioral disorders in newborns. Dendrimers can intrinsically target and deliver drugs for the treatment of neuroinflammation. We explore whether hydroxyl polyamidoamine (PAMAM) dendrimer (G4-OH)-based nanomedicines can be delivered to the fetus by intra-amniotic administration, in a mouse model of intrauterine inflammation. The time-dependent accumulation of G4-OH-fluorophore conjugate was quantified by fluorescence. These studies suggest that, after intra-amniotic administration, there is significant accumulation of dendrimer in the fetus gut and brain. In addition, there is some fetal-maternal transport of the dendrimer. Confocal microscopy confirmed the presence of G4-OH in the fetal brain, with a large accumulation in the brain blood vessels and the brain parenchyma, and some microglial uptake. We believe that intra-amniotic administration of G4-OH-drug nanomedicines may enable the treatment of diseases related to intrauterine inflammation and fetal neuroinflammation. From the Clinical Editor: Using a mouse model of intrauterin inflammation leading to neuroinflammation in the fetus, these investigators demonstrate that intra-amniotic delivery of hydroxyl polyamidoamine (PAMAM) dendrimer (G4-OH)-based nanomedicines may provide an effective method in preventing this complication.

Original languageEnglish (US)
Pages (from-to)1343-1351
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume10
Issue number6
DOIs
StatePublished - Aug 2014

Keywords

  • Biodistribution
  • Fetal brain
  • Intra-amniotic drug delivery
  • Intrauterine inflammation
  • PAMAM dendrimer

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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