Delivery and short-term maternal and fetal safety of vaginally administered PEG-PLGA nanoparticles.

At the onset of pregnancy, people with preexisting conditions face additional challenges in carrying their pregnancy to term, as the safety of the developing fetus and pregnant person is a significant factor of concern. Nanoparticle (NP)-based therapies have displayed success against various conditions and diseases in non-pregnant patients, but the use of NPs in maternal-fetal health applications needs to be better established. Local vaginal delivery of NPs is a promising administration route with the potential to yield high cargo retention in the vagina and improved therapeutic efficacy compared to systemic administration that results in rapid NP clearance by the hepatic first-pass effect. In this study, we investigated the biodistribution and short-term toxicity of poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs in pregnant mice following vaginal delivery. The NPs were either loaded with DiD fluorophores for tracking cargo distribution (termed DiD-PEG-PLGA NPs) or included Cy5-tagged PLGA in the formulation for tracking polymer distribution (termed Cy5-PEG-PLGA NPs). DiD-PEG-PLGA NPs were administered at gestational day (E)14.5 or 17.5, and cargo biodistribution was analyzed 24 h later by fluorescence imaging of whole excised tissues and histological sections. No gestational differences in DiD distribution were observed, so Cy5-PEG-PLGA NPs were administered at only E17.5 to evaluate polymer distribution in the reproductive organs of pregnant mice. Cy5-PEG-PLGA NPs distributed to the vagina, placentas, and embryos, whereas DiD cargo was only observed in the vagina. NPs did not impact maternal, fetal, or placental weight, suggesting they display no short-term effects on maternal or fetal growth. The results from this study encourage future investigation into the use of vaginally delivered NP therapies for conditions affecting the vagina during pregnancy.