Research: Nanoparticles for Delivery of Agents to Fetal Lungs

Acta Biomater

. 2021 Jan 20;S1742-7061(21)00052-0. doi: 10.1016/j.actbio.2021.01.024. Online ahead of print.

Nanoparticles for Delivery of Agents to Fetal Lungs

Sarah J Ullrich 1Mollie Freedman-Weiss 2Samantha Ahle 2Hanna K Mandl 3Alexandra S Piotrowski-Daspit 3Katherine Roberts 2Nicolas Yung 2Nathan Maassel 2Tory Bauer-Pisani 2Adele S Ricciardi 4Marie E Egan 5Peter M Glazer 6W Mark Saltzman 7David H Stitelman 2Affiliations expand

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Fetal treatment of congenital lung disease, such as cystic fibrosis, surfactant protein syndromes, and congenital diaphragmatic hernia, has been made possible by improvements in prenatal diagnostic and interventional technology. Delivery of therapeutic agents to fetal lungs in nanoparticles improves cellular uptake. The efficacy and safety of nanoparticle-based fetal lung therapy depends on targeting of necessary cell populations. This study aimed to determine the relative distribution of nanoparticles of a variety of compositions and sizes in the lungs of fetal mice delivered through intravenous and intra-amniotic routes. Intravenous delivery of particles was more effective than intra-amniotic delivery for epithelial, endothelial and hematopoietic cells in the fetal lung. The most effective targeting of lung tissue was with 250nm Poly-Amine-co-Ester (PACE) particles accumulating in 50% and 44% of epithelial and endothelial cells. This study demonstrated that route of delivery and particle composition impacts relative cellular uptake in fetal lung, which will inform future studies in particle-based fetal therapy.

Keywords: Biodegradable nanoparticles; Biodistribution; Fetal Therapy; Lung targeting.

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