Mir Asad, Acosta Teeshavi, Concheiro-Guisan Marta, Yellon Steven M, Patel Ketan, Reznik Sandra E
Department of Pharmaceutical Sciences, St. John's University, Queens, NY 11439, USA.
Department of Pharmaceutical Sciences, St. John's University, Queens, NY 11439, USA; Department of Sciences, John Jay College of Criminal Justice, City University of New York, 524 W 59th St, New York, NY 10019, USA.
Biochim Biophys Acta Mol Basis Dis. 2025 Jun;1871(5):167822. doi: 10.1016/j.bbadis.2025.167822. Epub 2025 Mar 31.
Vaginal administration and the uterine first pass effect allow for preferential delivery of drugs to the reproductive tract. Dimethylacetamide has previously been shown to delay preterm birth in a pregnant mouse model when given intraperitoneally but the effectiveness of a vaginal nanoformulation of dimethylacetamide has yet to be tested. The purpose of this study was to compare the two formulations of dimethylacetamide for efficacy in rescuing pups from preterm birth in an inflammation-induced mouse model, effects on the maternal fetal interface, and pharmacokinetic profiles in maternal plasma. Timed pregnant CD1 mice were given a 1.56 mg/kg intraperitoneal dose of lipopolysaccharide followed by 3 doses of either vaginal dimethylacetamide or intraperitoneal dimethylacetamide. Mice were monitored for 48 h and times of deliveries were recorded. Additionally, CD1 mice in late gestation were given a single dose of either vaginal or intraperitoneal dimethylacetamide and blood was drawn at 3 different time points following administration. Vaginal administration of dimethylacetamide had similar efficacy in delaying inflammation induced preterm birth as intraperitoneal administration but resulted in lower concentrations in the systemic circulation and decreased effects on the maternal fetal interface. Vaginal nanoformulations should be explored for their potential therapeutic value for the delay of preterm birth.
阴道给药和子宫首过效应可使药物优先输送至生殖道。先前研究表明，在孕鼠模型中腹腔注射二甲基乙酰胺可延迟早产，但二甲基乙酰胺阴道纳米制剂的有效性尚未得到测试。本研究的目的是比较两种二甲基乙酰胺制剂在炎症诱导的小鼠模型中挽救早产幼崽的疗效、对母胎界面的影响以及母体血浆中的药代动力学特征。对定时受孕的CD1小鼠腹腔注射1.56 mg/kg脂多糖，随后给予3剂阴道二甲基乙酰胺或腹腔二甲基乙酰胺。对小鼠监测48小时并记录分娩时间。此外，对妊娠晚期的CD1小鼠单次给予阴道或腹腔二甲基乙酰胺，并在给药后的3个不同时间点采集血液。阴道给予二甲基乙酰胺在延迟炎症诱导的早产方面与腹腔给药具有相似的疗效，但导致全身循环中的浓度较低，并降低了对母胎界面的影响。应探索阴道纳米制剂在延迟早产方面的潜在治疗价值。
