Folate-mediated Transport of Nanoparticles across the Placenta

Abstract

Background: In this study, a prototype of a targeted nanocarrier for drug delivery for prenatal therapy of the developing fetus was developed and examined in vitro and ex vivo. The folate transport mechanism in the human placenta was utilized as a possible pathway for the transplacental delivery of targeted nanoparticles. Methods: Several types of folic acid-decorated polymeric nanoparticles were synthesized and characterized. During transport studies of targeted and non-targeted fluorescent nanoparticles across the placental barrier, the apparent permeability values, uptake, transfer indices, and distribution in placental tissue were determined. Results: The nanoparticles had no effect on BeWo b30 cell viability. In vitro, studies showed significantly higher apparent permeability of the targeted nanoparticles across the cell monolayers as compared to the nontargeted nanoparticles (Pe = 5.92 ± 1.44 ×10-6 cm/s for PLGA-PEG-FA vs. 1.26 ± 0.31 ×10-6 cm/s for PLGA-PEG, P < 0.05), and the transport of the targeted nanoparticles was significantly inhibited by excess folate. Ex vivo placental perfusion showed significantly greater accumulation of the targeted nanoparticles in the placental tissue (4.31 ± 0.91%/g for PLGA-PEG-FA vs. 2.07 ± 0.26%/g for PLGA-PEG). Conclusion: The data obtained suggested different mechanisms for the uptake and transplacental transfer of targeted versus nontargeted nanoparticles. This targeted nanoformulation may be a promising strategy for fetal drug therapy.