Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth

Hannah C. Zierden, Jairo I. Ortiz, Kevin DeLong, Jingqi Yu, Gaoshan Li, Peter Dimitrion, Sabrine Bensouda, Victoria Laney, Anna Bailey, Nicole M. Anders, Morgan Scardina, Mala Mahendroo, Sam Mesiano, Irina Burd, Gunter Wagner, Justin Hanes, Laura M. Ensign

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammation contributes to nearly 4 million global premature births annually. Here, we used a mouse model of intrauterine inflammation to test clinically used formulations, as well as engineered nanoformulations, for the prevention of preterm birth (PTB). We observed that neither systemic 17a-hydroxyprogesterone caproate (Makena) nor vaginal progesterone gel (Crinone) was sufficient to prevent inflammation-induced PTB, consistent with recent clinical trial failures. However, we found that vaginal delivery of mucoinert nanosuspensions of histone deacetylase (HDAC) inhibitors, in some cases with the addition of progesterone, prevented PTB and resulted in delivery of live pups exhibiting neurotypical development. In human myometrial cells in vitro, the P4/HDAC inhibitor combination both inhibited cell contractility and promoted the anti-inflammatory action of P4 by increasing progesterone receptor B stability. Here, we demonstrate the use of vaginally delivered drugs to prevent intrauterine inflammation-induced PTB resulting in the birth of live offspring in a preclinical animal model.

Original languageEnglish (US)
Article numbereabc6245
JournalScience translational medicine
Volume13
Issue number576
DOIs
StatePublished - Jan 1 2021

ASJC Scopus subject areas

  • Medicine(all)

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