Prenatal Intraportal Delivery of Polymeric Nanoparticles to Fetal Rhesus Monkeys (Macaca mulatta).

Preliminary investigations focused on biodistribution of polymeric nanoparticles (NPs) shortly after ultrasound-guided delivery via the portal vein in early second-trimester fetal rhesus monkeys. Results demonstrated that poly(lactic-co-glycolic acid) (PLGA) NPs (N = 3; 3 mg administered at 75-80 days gestational age) and poly(amine-co-ester)-polyethylene glycol (PACE-PEG) NPs (N = 3; 3 mg at 75-80 days gestational age) distributed to fetal tissues when assessed 24 h post-administration. No adverse findings were observed. PLGA NPs were found primarily in the fetal liver and spleen, whereas PACE-PEG NPs showed more widespread biodistribution to a range of anatomical sites. In another fetal subset with PACE-PEG NPs (N = 2; 90 days gestational age) assessed within 48-h post-administration, results demonstrated enhanced green fluorescent protein reporter mRNA expression in select tissues. These early-stage short-term studies suggest that polymeric NPs, particularly those composed of PACE-PEG, can be safely administered and are potential candidates for fetal delivery of therapeutic nucleic acids. While preliminary, these studies provide evidence to support further investigations in this species to address long-term safety and efficiency.