title: Uterus-targeted liposomes for preterm labor management: studies in pregnant mice.
abstract: Preterm labor caused by uterine contractions is a major contributor to neonatal morbidity and mortality. Treatment intended to reduce uterine contractions include tocolytic agents, such as indomethacin. Unfortunately, clinically used tocolytics are frequently inefficient and cross the placenta causing fetal side effects. Here we show for the first time in obstetrics the use of a targeted nanoparticle directed to the pregnant uterus and loaded with a tocolytic for reducing its placental passage and sustaining its efficacy. Nanoliposomes encapsulating indomethacin and decorated with clinically used oxytocin receptor antagonist were designed and evaluated in-vitro, ex-vivo and in-vivo. The proposed approach resulted in targeting uterine cells in-vitro, inhibiting uterine contractions ex-vivo, while doubling uterine drug concentration, decreasing fetal levels, and maintaining the preterm birth rate in vivo in a pregnant mouse model. This promising approach opens new horizons for drug development in obstetrics that could greatly impact preterm birth, which currently has no successful treatments.
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Jerrie S
authors.initials: JS
authors.lastname: Refuerzo
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Fransisca
authors.initials: F
authors.lastname: Leonard
authors.affiliation: Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Bulayeva
authors.affiliation: Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gorenstein
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology at University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Chiossi
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ontiveros
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Longo
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Biana
authors.initials: B
authors.lastname: Godin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004339:Drug Compounding; D005260:Female; D015870:Gene Expression; D006727:Hormone Antagonists / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D011485:Protein Binding; D018045:Receptors, Oxytocin / Q000378:metabolism; D015149:Tocolytic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism; D014668:Vasotocin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
chemical_list: D006727:Hormone Antagonists; D008081:Liposomes; D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; C047046:atosiban; D014668:Vasotocin; D007213:Indomethacin