Research ArticlePreterm Birth

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

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Science Translational Medicine  13 Jan 2021:
Vol. 13, Issue 576, eabc6245
DOI: 10.1126/scitranslmed.abc6245

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Drug delivery to delay delivery

Preterm birth, often caused by inflammation, is a major contributor to infant morbidity and mortality. It often cannot be predicted, but even for women who are known to be at risk of preterm delivery, there is no currently approved intervention to prevent it, although progesterone-based interventions are sometimes attempted. To improve access of treatments to the appropriate tissues for preventing preterm delivery, Zierden et al. designed a mucoinert nanosuspension to optimize vaginal dosing of therapeutics. The authors demonstrated the effectiveness of their approach in mouse models using histone deacetylase inhibitors with and without progesterone. Their approach improved the rates of full-term delivery of neurotypical pups.

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.

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