title: Liposome-encapsulated hemoglobin (hemoglobin-vesicle) is not transferred from mother to fetus at the late stage of pregnancy in the rat model.
abstract: OBJECTIVE
  Liposome-encapsulated hemoglobin (hemoglobin vesicles: HbV; diameter 250 nm) is reconstructed from human hemoglobin and developed as an artificial oxygen carrier for use as a transfusion alternative. Previous studies using rodent models closely investigated the safety of daily repeated infusions (DRI) of HbV and reported that the reticuloendothelial system was physiologically capable of degrading HbV to maintain plasma clinical chemistry within normal ranges. The present study examined the effect of DRI of HbV on the pregnant rat mother and fetal development, focusing on placental transfer of HbV in pregnancy.
  
  
  METHODS
  Pregnant rats intravenously received HbV bolus injections at 2 ml/kg/day for the last 7 consecutive days till term. The cumulative infusion volume (14 ml/kg) was equal to 25% of the whole blood volume (56 ml/kg).
  
  
  RESULTS
  Maternal DRI of HbV had no obvious side effects on the pregnant mother or on fetal development. Maternal vital signs, plasma clinical chemistry, and blood gas parameters were overall normal after DRI of HbV. In addition, maternal/fetal transfer of HbV was limited to the placenta and HbV did not reach the fetus. Histopathological examination with human hemoglobin antibody detected HbV accumulation in the maternal spleen, liver, kidney, and placenta, but not in the fetuses. These results were also confirmed by a pharmacokinetic study using (125)I-labeled HbV.
  
  
  CONCLUSIONS
  This safety study of HbV use in the pregnant mother and fetus will contribute to a possible application of HbV as a potential treatment for fetal hypoxia by supplying oxygen through the placenta.
authors.affiliation: Center for Perinatal Medicine, Tohoku University Hospital, Sendai, Japan; Department of Pediatrics, Tohoku University Hospital, Sendai, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Kaga
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Perinatal Medicine, Tohoku University Hospital, Sendai, Japan; Department of Pediatrics, Tohoku University Hospital, Sendai, Japan; Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan; Department of Obstetrics and Gynecology, Tohoku University Hospital, Sendai, Japan. Electronic address: hideohta@ncnp.go.jp.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Department of Biopharmacetutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Biopharmacetutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ogaki
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Izumi
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Inagaki
authors.affiliation: Department of Pediatrics, Tohoku University Hospital, Sendai, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuchiya
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Okamura
authors.affiliation: Department of Biopharmacetutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.affiliation: Waseda Bioscience Research Institute in Singapore, Biopolis, Republic of Singapore.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Center for Perinatal Medicine, Tohoku University Hospital, Sendai, Japan; Department of Obstetrics and Gynecology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
mesh_terms: D000818:Animals; D005260:Female; D047109:Fetal Development; D005333:Fetus / Q000737:chemistry; D006454:Hemoglobins / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000737:chemistry; D008081:Liposomes; D008099:Liver / Q000737:chemistry; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000737:chemistry
chemical_list: D006454:Hemoglobins; D008081:Liposomes