Characterizing The Biodistribution Of Intravenously And Intra-amniotically Injected Nanoparticles In Rat Fetuses
*Samantha L Ahle1, *James S. Farrelly1, *Adele S Ricciardi1, *Valerie S Luks1, *W. Mark Saltzman2, *David H. Stitelman1
1Yale School of Medicine, New Haven, CT;2Yale School of Engineering and Applied Science, New Haven, CT
Objective: Determine the biodistribution of fluorescently-tagged nanoparticles (NPs) injected intravenously (IV) or intra-amniotically (IA) into rat fetuses.
Design: Non-randomized control trial
Setting: Laboratory
Patients: Rats
Interventions: Under anesthesia, laparotomies were performed on pregnant rats at varied time points from gestational age (E) 16-20 days. Using a micropipette, rat fetuses were injected with poly(lactide-co-glycolide) (PLGA) NPs loaded with green fluorescent dye (DiO) either into the amniotic cavity or through the vitelline vein. Three hours later the rat fetuses were sacrificed. The tissues were examined using confocal microscopy to determine particle distribution.
Main Outcome Measures: Biodistribution of PLGA NPs
Results: The distribution of NPs was evidenced by viewing the green fluorescent dye on microscopy of tissue from injected fetuses compared to tissue from uninjected fetuses. IV injections were performed successfully from days E16-18, and NPs were distributed to lung, liver, and gastrointestinal tract, but were not found in skin or brain. Successful IA injections were performed at ages ranging from E16-E20. Particle distribution to the lung was not observed at early ages, but was observed at E19, suggesting this is when the fetuses start to breathe and swallow.Conclusions: We are interested in delivering therapeutic agents packaged in NPs, to developing fetuses in utero to alter development. Characterizing the biodistribution of NPs is paramount prior to delivering NPs loaded with therapeutic agents. This study reveals that in rats, NP delivery throughout the fetus is most successful with IV injection; however NP delivery to lungs does occur at E19 and later via IA injection. 
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