TY - JOUR
T1 - Folate-mediated Transport of Nanoparticles across the Placenta
AU - Kalashnikova, Irina
AU - Patrikeeva, Svetlana
AU - Nanovskaya, Tatiana N.
AU - Andreev, Yaroslav A.
AU - Ahmed, Mahmoud S.
AU - Rytting, Erik
N1 - Publisher Copyright:
© 2024 Bentham Science Publishers.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - folate receptors
KW - folic acid
KW - Nanomedicine
KW - placenta
KW - PLGA nanoparticles
KW - targeted drug delivery
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U2 - 10.2174/2211738511666230717122429
DO - 10.2174/2211738511666230717122429
M3 - Article
C2 - 37461351
AN - SCOPUS:85187162551
SN - 2211-7385
VL - 12
SP - 171
EP - 183
JO - Pharmaceutical Nanotechnology
JF - Pharmaceutical Nanotechnology
IS - 2
ER -