Preterm labor, leading to preterm birth (birth prior to 37 weeks of pregnancy) is a leading cause of perinatal morbidity and mortality affecting estimated 15 million births worldwide annually. Since the fetus is not yet fully developed before 37 weeks of pregnancy, health problems associated with preterm birth include a variety of acute and chronic health/developmental deficiencies. Among these are acute respiratory, gastrointestinal, immunologic, CNS, hearing and vision issues, as well as cerebral palsy, cognitive, visual, hearing, behavioral, social-emotional, learning, health, and growth problems. Indomethacin (IND) is a tocolytic that prevents uterine contractions and, thus, preterm birth, improving neonatal outcomes. Unfortunately, this efficient tocolytic is limited in its use due to associated cardiac, renal, neurological and other toxicities to the fetus. Fetal exposure to harmful medications is based on the ability of drug molecules to pass transplacentally from mother to fetus, which commonly involves simple passive diffusion. Having a low-molecular weight IND readily crosses the placenta as reflected in complications related to the fetal exposure to the drug. We have designed a liposomal delivery system (LIP) of IND that is targeted to the uterus through oxytocin receptor antagonist (ORA) expressed on the pregnant myometrium, thus increasing the concentration of the agent in the affected organ and minimizing the circulating free drug fraction available for placental passage. LIP-IND-ORA system design, in vitro studies in primary human uterine cells, ex vivo contractility studies in human myometrium strips and in vivo biodistribution and efficacy studies in pregnant rodents will be discussed.
Audience take away:
• The use of nanomedicine in the field of obstetrics is a novel topic
• We believe that using nanocarriers for preventing the translacental passage of medications can open new avenues for safer therapeutics in the preganancy.
• Additionally, we have used a currently existing medication of targeting our system, which can significantly decrease the path to the regulatory approval. These concepts can also be used in other fields.
• In the presentation I will also briefly discus the pathway we are undertaking for initiating clinical studies with this delivery system.