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CME Credit Offered
CME Credit Offered
Abstract Award
Abstract Award
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Poster Session 3

(714) Nanoparticle-based fetal Intraperitoneal injection is an alternative to intravascular drug delivery to the pulmonary endothelium

Friday, January 31, 2025
10:30 AM – 12:30 PM  
Objective:  Fetal intravascular injection of nanoparticle-based therapy is proposed as a technique for targeted in-utero therapies. However, in humans, umbilical cord access is limited both by gestational age and physician skillset, thus limiting the application of emerging therapies. Specifically in disorders of the fetal lungs, critical phases of development would be missed by waiting for the opportunity for umbilical cord access. Intraperitoneal transfusions have been used in early pregnancy when intravascular access is not feasible, therefore we sought to assess the feasibility of fetal intraperitoneal nanoparticle injections.

Study Design:

Polyethylenimine-(5) myristic acid/ poly(ethylene glycol)-oleic acid/cholesterol (PEI-PEG) nanoparticles were created as per prior publications and were tagged with fluorescent-AF647 Dylight. Pregnant rats underwent midline laparotomy at E17.5-E18.5 to fetal injection. Three arms were pre-determined, either fetal intraperitoneal injection of nanoparticles, intra-amniotic injection of nanoparticles, or sham. Fetuses were harvested at E20.5 and cells were immediately isolated and sorted via flow cytometry. As these nanoparticles localize to the pulmonary endothelium in newborn rodents, flow cytometry was used to evaluate pulmonary vascular endothelial cell uptake.

Results: Cell sorting successfully isolated fetal lung tissue and CD31+ CD45- cell lines were considered pulmonary vascular endothelium. Pulmonary endothelium of fetuses that underwent intraperitoneal injection were found to have 50.2% of cells positive for Dylight, vs 0.2% in fetuses that had intra-amniotic injection and 0.0% in control (p < 0.001), Figure 1.  Every fetus that had an intraperitoneal injection had at least 42% of pulmonary endothelial cells with nanoparticles present, and no intra-amniotic injection had greater than 1%.

Conclusion: Fetal intraperitoneal injection of PEI-PEG nanoparticles successfully targets pulmonary endothelium. IP injections of PEI-PEG nanoparticles provides a vehicle for targeted treatment of the fetal lungs early in gestation.