Folate-mediated Transport of Nanoparticles across the Placenta

Irina Kalashnikova, Svetlana Patrikeeva, Tatiana N. Nanovskaya, Yaroslav A. Andreev, Mahmoud S. Ahmed, Erik Rytting

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In this study, a prototype of a targeted nanocarrier for drug delivery for prena-tal 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 character-ized. 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 com-pared 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.

Original languageEnglish (US)
Pages (from-to)171-183
Number of pages13
JournalPharmaceutical Nanotechnology
Volume12
Issue number2
DOIs
StatePublished - 2024
Externally publishedYes

Keywords

  • folate receptors
  • folic acid
  • Nanomedicine
  • placenta
  • PLGA nanoparticles
  • targeted drug delivery

ASJC Scopus subject areas

  • Biomedical Engineering
  • Pharmaceutical Science

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