ABSTRACT Based on World Health Organization estimates, the annual rate of preterm birth (PTB) is greater than 10% in the majority of countries. Premature birth before 37 completed weeks of gestation is the leading cause of mortality in the first year of life and is associated with morbidity that has life-long cognitive consequences. Acute and lifespan care costs associated with preterm births have broad and sustained effects on families and are enormously expensive for society. Causes of PTB are multifactorial, but the single most common cause of PTB is inflammation. Sadly, there is currently no United States Food and Drug Administration approved drug for the prevention of PTB. One of the hurdles in translational research and drug development in this field is the risk of drug related toxicity affecting the fetus. Several years ago, we made the fortuitous discovery that the safe pharmaceutical solvent, N,N-dimethylacetamide (DMA), prevents PTB and rescues pups from spontaneous abortion in our mouse model. Further studies in our laboratory revealed that DMA suppresses nuclear translocation and activation of nuclear factor kappa B (NF-kB), a transcription factor that regulates immune cell-mediated inflammation. In addition, we have shown that DMA attenuates cytokine secretion from cultured human trophoblasts and from human placental explants. Recently, our laboratory has teamed up with our collaborator’s to develop a vaginal (pv) self-nanoemulsifying drug delivery system (SNEDDS), which takes advantage of the first uterine/cervix pass effect to deliver drugs introduced into the vaginal cavity directly to the cervix and uterus, thereby minimizing risk of systemic toxicity and teratogenicity. The specific aims of the current project are to 1) test the effects of our pv DMA SNEDDS on histomorphology and inflammatory responses in the cervix in a murine model; 2) determine the molecular mechanism whereby DMA inhibits NF-kB transcriptional activity; and 3) compare toxic and teratogenic effects of a DMA SNEDDS to intraperitoneal administration of DMA. To accomplish these aims, we assembled a team of experts in PTB, cervix histomorphology and drug formulation. This multidisciplinary team will be working alongside our students, who come from a diverse and underserved population. Although PTB is a global public health problem, rates of PTB are significantly higher among underserved populations. The novelty of re-purposing a readily available and inexpensive common drug excipient to prevent PTB, together with designing a vaginal formulation that can be administered by patients remote from clinics or hospitals, addresses a critical gap in the field of drug development for PTB.