Investigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery

When exposed to the biological environment, nanoparticles (NPs) form a protein corona that influences delivery profile. We present a study of protein corona formation and NP biodistribution in amniotic fluid (AF) for poly(lactic-co-glycolic acid) (PLGA) and poly(lactic-acid) (PLA) NPs, with and without polyethylene glycol (PEG), as well as poly(amine-co-ester)-PEG (PACE-PEG) NPs. The presence of surface PEG and polyvinyl alcohol (PVA) were characterized to investigate surfactant role in determining protein corona formation. The surface density of PEG groups demonstrated an inverse correlation with the total amount of protein surface adsorption. All PEGylated NPs exhibited a dense brush conformation and demonstrated higher levels of stability in AF than non-PEGylated NPs. The protein corona composition varied by core polymer, while the amount of protein adsorption varied by PEGylation status. In A549 cells, in vitro cellular association of each NP type correlated with the amount of albumin that was found in the protein corona. In vivo, only PEGylated NPs were able successfully distribute to fetal organs, likely due to the enhanced stability imparted by PEG. PLGA-PEG and PACE-PEG NPs had both high levels of albumin in the protein corona and high biodistribution to the fetal lung, consistent with the association with lung cells in vitro. PLA-PEG NPs distributed exclusively to the fetal bowel, which we propose is associated with known gastrointestinal targeting keratin proteins. By furthering our understanding of polymeric NP behavior in AF, this novel study provides a basis for optimization of intra-amniotic NP delivery systems targeting congenital pulmonary and gastrointestinal diseases.