title: Fetal uptake of intra-amniotically delivered dendrimers in a mouse model of intrauterine inflammation and preterm birth.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Integrated Research Center for Fetal Medicine, Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD. Electronic address: iburd@jhmi.edu.
authors.forename: Irina
authors.initials: I
authors.lastname: Burd
authors.affiliation: Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Integrated Research Center for Fetal Medicine, Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Tahani
authors.initials: T
authors.lastname: Dada
authors.affiliation: Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Mishra
authors.affiliation: Integrated Research Center for Fetal Medicine, Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Talaibek
authors.initials: T
authors.lastname: Borbiev
authors.affiliation: Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Wojciech G
authors.initials: WG
authors.lastname: Lesniak
authors.affiliation: Integrated Research Center for Fetal Medicine, Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Haitham
authors.initials: H
authors.lastname: Baghlaf
authors.affiliation: Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Kannan
authors.affiliation: Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD. Electronic address: krangar1@jhmi.edu.
authors.forename: Rangaramanujam M
authors.initials: RM
authors.lastname: Kannan
mesh_terms: D000650:Amnion / Q000378:metabolism*; D000818:Animals; D050091:Dendrimers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D047928:Premature Birth / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D014599:Uterus / Q000473:pathology
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst
keywords: Biodistribution; Fetal brain; Intra-amniotic drug delivery; Intrauterine inflammation; PAMAM dendrimer