# Nanomedicine approaches for prevention of inflammation-induced preterm birth > **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $72,214 ## Abstract PROJECT SUMMARY Preterm birth (PTB), or birth before 37 weeks of gestation, was the second leading cause of infant death in the US in 2017. Each year, more than $26 billion is spent on treatment and care of babies born prematurely, not accounting for the lifelong impact of developmental and cognitive impairments. Here, we focus on the most common cause of PTB, inflammation. Maternal inflammation triggers a pro-inflammatory cytokine response that can also lead to fetal inflammatory response syndrome and perinatal brain injury. Brain injury leads to a spectrum of adverse neurobehavioral outcomes, including cerebral palsy, autism, schizophrenia, and cognitive delay among others. The only approved drug for prevention of PTB is the synthetic progestin hydroxyprogesterone caproate (OHPC) dosed systemically as weekly injections in women with a singleton pregnancy with a history of singleton spontaneous PTB, and a recently failed confirmatory study has led to calls for the FDA to withdraw the drug from the market. For women that are already in preterm labor, off-label tocolytics (anti-contraction medications) may be given to slow uterine contractions, but this typically only delays birth for a few days. New, effective treatments for preventing PTB are desperately needed. Further, the vaginal route of administration is underexplored but highly promising; vaginally absorbed drug is preferentially transported to the uterus. We have demonstrated that by increasing mucosal drug penetration and eliminating hypertonic excipients that cause local toxicity, increased drug delivery to target reproductive tissues can be achieved. In the setting of intrauterine inflammation, we have observed that combining vaginal progesterone (P4) with drugs that favor non-laboring states of P4 receptor and gene expression, such as histone deacetylase inhibitors (HDACi), provides a significant increase in dams that go on to deliver live pups. In contrast, dosing the same drug combination systemically or injecting the approved product OHPC had no therapeutic effect. Analysis of gene expression changes suggest that quiescing myometrial activity was key, and we have confirmed that the myometrial tissue levels of P4 and HDACi measured after vaginal combination delivery in mice were also the most effective in preventing human myometrial cell contractility. Importantly, preliminary neurobehavioral analysis of pups born after exposure to intrauterine inflammation followed by vaginal P4/HDACi suggests that development occurred similar to pups that had not been exposed to intrauterine inflammation. Herein, we propose studies that use in vitro assays for assessing the potential of kinase inhibitors as a drug class for repurposing in PTB prevention. Candidate drugs will be screened for inhibition of myometrial contractility in human myometrial cell culture, and downstream effects on inflammatory signaling will be assessed. The most effective drugs will then be formulated for vaginal administr... ## Key facts - **NIH application ID:** 10406669 - **Project number:** 3R01HD103124-01A1S2 - **Recipient organization:** JOHNS HOPKINS UNIVERSITY - **Principal Investigator:** IRINA BURD - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $72,214 - **Award type:** 3 - **Project period:** 2021-04-13 → 2026-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10406669 ## Citation > US National Institutes of Health, RePORTER application 10406669, Nanomedicine approaches for prevention of inflammation-induced preterm birth (3R01HD103124-01A1S2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10406669. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*