Abstract
At the onset of pregnancy, people with preexisting conditions face additional challenges in carrying their pregnancy to term, as the safety of the develo** 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.
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Acknowledgements
The authors thank Shannon Modla for assistance acquiring TEM images and Maneesha Sahni for assistance with Cy5-PEG-PLGA NP synthesis.
Funding
This work was supported by the National Institutes of Health under grant numbers R35GM119659 (ESD), U54GM104941 (ESD, JPG), U19AI158930 (JPG) and T32GM133395 and F31HD105398 (KMN). NIC received support from the University Graduate Scholars Program. TEM access was supported by grants from the NIH-NIGMS P20 GM103446, the NSF (IIA-1301765) and the State of Delaware. The content of this article is solely the responsibility of the authors and does not necessarily reflect the views of the funding agencies.
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All authors contributed to study conception and design. Material preparation, data collection, and analysis were performed by N’Dea Irvin-Choy and Katherine Nelson, co-first authors of this manuscript. The first draft of the manuscript was written by N’Dea Irvin-Choy and Katherine Nelson and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Funding acquisition and project supervision were performed by Emily Day and Jason Gleghorn, the co-corresponding authors.
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Irvin-Choy, N.S., Nelson, K.M., Gleghorn, J.P. et al. Delivery and short-term maternal and fetal safety of vaginally administered PEG-PLGA nanoparticles. Drug Deliv. and Transl. Res. 13, 3003–3013 (2023). https://doi.org/10.1007/s13346-023-01369-w
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DOI: https://doi.org/10.1007/s13346-023-01369-w