TY - JOUR
T1 - Fetal uptake of intra-amniotically delivered dendrimers in a mouse model of intrauterine inflammation and preterm birth
AU - Burd, Irina
AU - Zhang, Fan
AU - Dada, Tahani
AU - Mishra, Manoj K.
AU - Borbiev, Talaibek
AU - Lesniak, Wojciech G.
AU - Baghlaf, Haitham
AU - Kannan, Sujatha
AU - Kannan, Rangaramanujam M.
N1 - Funding Information:
This work was supported by Aramco Services Company fund (IB), NICHD K08HD073315 (IB), and NICHD R01 HD069562-01A1 (SK).
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Biodistribution
KW - Fetal brain
KW - Intra-amniotic drug delivery
KW - Intrauterine inflammation
KW - PAMAM dendrimer
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U2 - 10.1016/j.nano.2014.03.008
DO - 10.1016/j.nano.2014.03.008
M3 - Article
C2 - 24657482
AN - SCOPUS:84905276133
SN - 1549-9634
VL - 10
SP - 1343
EP - 1351
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 6
ER -