Assessment of dually labelled PEGylated liposomes transplacental passage and placental penetration using a combination of two ex-vivo human models: the dually perfused placenta and the suspended villous explants

Valero, Lucie; Alhareth, Khair; Gil, Sophie; Simasotchi, Christelle; Roques, Caroline; Scherman, Daniel; Mignet, Nathalie; Fournier, Thierry; Andrieux, Karine

doi:10.1016/j.ijpharm.2017.07.076

Cited by 24 publications

(18 citation statements)

References 37 publications

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“…In our first study, we showed that liposomes are good candidates as vectors for placental drug delivery thanks to their interaction with the syncytiotrophoblast without the transfer of formulation components to the fetus [ 8 ]. In this study, we demonstrate that siRNA loaded into lipoplexes are internalized by VCT.…”

Section: Discussionmentioning

confidence: 99%

“…We listed and discussed in a recent review the potential of nanomedicine, and particularly liposomes, to empower new strategies for the treatment of preeclampsia, one of the most severe pregnancy complications often responsible for prematurity [ 7 ]. We recently reported that PEGylated liposomes penetrate the outer cell layer of the placenta without gaining access to the fetal circulation [ 8 ]. This finding support the potential of liposomes as carriers of therapeutic molecules, including gene therapy agents, such as small interfering RNA (siRNA).…”

Section: Introductionmentioning

confidence: 99%

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Liposomes as Gene Delivery Vectors for Human Placental Cells

et al. 2018

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Nanomedicine as a therapeutic approach for pregnancy-related diseases could offer improved treatments for the mother while avoiding side effects for the fetus. In this study, we evaluated the potential of liposomes as carriers for small interfering RNAs to placental cells. Three neutral formulations carrying rhodamine-labelled siRNAs were evaluated on an in vitro model, i.e., human primary villous cytotrophoblasts. siRNA internalization rate from lipoplexes were compared to the one in the presence of the lipofectamine reagent and assessed by confocal microscopy. Results showed cellular internalization of nucleic acid with all three formulations, based on two cationic lipids, either DMAPAP or CSL-3. Moreover, incubation with DMAPAP+AA provided a rate of labelled cells as high as with lipofectamine (53 ± 15% and 44 ± 12%, respectively) while being more biocompatible. The proportion of cells which internalized siRNA were similar when using DMAPAP/DDSTU (16 ± 5%) and CSL-3 (22 ± 5%). This work highlights that liposomes could be a promising approach for gene therapy dedicated to pregnant patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Liposomes as Gene Delivery Vectors for Human Placental Cells

et al. 2018

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“…Random harvested villi from term placentae, dissected as above, with a similar weight, were hung on needles and completely immerged in OptiMem media (Phenol Red-free, Gibco) as hanging villi, for 24 and 48 h, in 24-wells plates (Corning, Schiphol-Rijk, Netherlands) developed by SA Degrelle as previously described [64].…”

Section: Methodsmentioning

confidence: 99%

Expression, Localization, and Activity of the Aryl Hydrocarbon Receptor in the Human Placenta

Wakx

Nedder

Tomkiewicz-Raulet

et al. 2018

IJMS

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The human placenta is an organ between the blood of the mother and the fetus, which is essential for fetal development. It also plays a role as a selective barrier against environmental pollutants that may bypass epithelial barriers and reach the placenta, with implications for the outcome of pregnancy. The aryl hydrocarbon receptor (AhR) is one of the most important environmental-sensor transcription factors and mediates the metabolism of a wide variety of xenobiotics. Nevertheless, the identification of dietary and endogenous ligands of AhR suggest that it may also fulfil physiological functions with which pollutants may interfere. Placental AhR expression and activity is largely unknown. We established the cartography of AhR expression at transcript and protein levels, its cellular distribution, and its transcriptional activity toward the expression of its main target genes. We studied the profile of AhR expression and activity during different pregnancy periods, during trophoblasts differentiation in vitro, and in a trophoblast cell line. Using diverse methods, such as cell fractionation and immunofluorescence microscopy, we found a constitutive nuclear localization of AhR in every placental model, in the absence of any voluntarily-added exogenous activator. Our data suggest an intrinsic activation of AhR due to the presence of endogenous placental ligands.

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“…Different media compositions were used in placental perfusion studies of nanomaterials, depending on the addressed research question [30,41,66,67]. Our findings demonstrate, for the first time, a protein-specific and medium dependent PS-uptake into and/or adherence of particles to placental tissue.…”

Section: Discussionmentioning

confidence: 73%

Plasma proteins facilitates placental transfer of polystyrene particles

et al. 2020

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Background Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. In addition to dimension, charge and material the distinct protein corona influences the interplay of nanoparticles with tissue barriers. In this study we were focused on the impact of in situ formed human plasma protein corona on the transfer of 80 nm polystyrene nanoparticles (PS-particles) across the human placenta. To study materno-to fetal PS transfer we used the human ex vivo placental perfusion approach, which represents an intact and physiological tissue barrier. To analyze the protein corona of PS particles we performed shotgun proteomics of isolated nanoparticles before and after tissue exposure. Results Human plasma incubated with PS-particles of 80 nm and subsequent formed protein corona enhanced the transfer across the human placenta compared to PS-corona formed by bovine serum albumin and dextran which served as a control. Quantitative and qualitative changes of plasma proteins determined the changes in PS transfer across the barrier. Based on the analysis of the PS-proteome two candidate proteins, namely human albumin and immunoglobulin G were tested if these proteins may account for the enhanced PS-transfer across the placenta. Interestingly, the protein corona formed by human albumin significantly induced the transfer of PS-particles across the tissue compared to the formed IgG-corona. Conclusion In total we demonstrate the PS corona dynamically and significantly evolves upon crossing the human placenta. Thus, the initial composition of PS particles in the maternal circulation is not predictive for their transfer characteristics and performance once beyond the barrier of the placenta. The precise mechanism of these effects remains to be elucidated but highlights the importance of using well designed biological models when testing nanoparticles for biomedical applications.

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Assessment of dually labelled PEGylated liposomes transplacental passage and placental penetration using a combination of two ex-vivo human models: the dually perfused placenta and the suspended villous explants

Cited by 24 publications

References 37 publications

Liposomes as Gene Delivery Vectors for Human Placental Cells

Liposomes as Gene Delivery Vectors for Human Placental Cells

Expression, Localization, and Activity of the Aryl Hydrocarbon Receptor in the Human Placenta

Plasma proteins facilitates placental transfer of polystyrene particles

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