Uterus-targeted liposomes for preterm labor management: Studies in pregnant mice

Jerrie S. Refuerzo, Fransisca Leonard, Nataliya Bulayeva, David Gorenstein, Giuseppe Chiossi, Alejandra Ontiveros, Monica Longo, Biana Godin

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Article number34710
JournalScientific Reports
Volume6
DOIs
StatePublished - Oct 11 2016

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Tocolytic Agents
Uterine Contraction
Premature Obstetric Labor
Liposomes
Uterus
Premature Birth
Indomethacin
Obstetrics
Oxytocin Receptors
Birth Rate
Infant Mortality
Pharmaceutical Preparations
Nanoparticles
Placenta
Morbidity
Therapeutics
In Vitro Techniques

ASJC Scopus subject areas

  • General

Cite this

Refuerzo, J. S., Leonard, F., Bulayeva, N., Gorenstein, D., Chiossi, G., Ontiveros, A., ... Godin, B. (2016). Uterus-targeted liposomes for preterm labor management: Studies in pregnant mice. Scientific Reports, 6, [34710]. https://doi.org/10.1038/srep34710

Uterus-targeted liposomes for preterm labor management : Studies in pregnant mice. / Refuerzo, Jerrie S.; Leonard, Fransisca; Bulayeva, Nataliya; Gorenstein, David; Chiossi, Giuseppe; Ontiveros, Alejandra; Longo, Monica; Godin, Biana.

In: Scientific Reports, Vol. 6, 34710, 11.10.2016.

Research output: Contribution to journalArticle

Refuerzo, JS, Leonard, F, Bulayeva, N, Gorenstein, D, Chiossi, G, Ontiveros, A, Longo, M & Godin, B 2016, 'Uterus-targeted liposomes for preterm labor management: Studies in pregnant mice', Scientific Reports, vol. 6, 34710. https://doi.org/10.1038/srep34710
Refuerzo JS, Leonard F, Bulayeva N, Gorenstein D, Chiossi G, Ontiveros A et al. Uterus-targeted liposomes for preterm labor management: Studies in pregnant mice. Scientific Reports. 2016 Oct 11;6. 34710. https://doi.org/10.1038/srep34710
Refuerzo, Jerrie S. ; Leonard, Fransisca ; Bulayeva, Nataliya ; Gorenstein, David ; Chiossi, Giuseppe ; Ontiveros, Alejandra ; Longo, Monica ; Godin, Biana. / Uterus-targeted liposomes for preterm labor management : Studies in pregnant mice. In: Scientific Reports. 2016 ; Vol. 6.
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