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Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta
Pregnant women are still considered as drug orphans. Developing new medications for pregnancy complications is an urgent need. Nanomedicines seem to be a promising approach to control the biodistribution of drugs to ensure both the mother’s and the fetus’ safety. Understanding the interaction betwee...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181748/ https://www.ncbi.nlm.nih.gov/pubmed/35682978 http://dx.doi.org/10.3390/ijms23116299 |
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author | Fliedel, Louise Alhareth, Khair Seguin, Johanne El-Khashab, Marwa Chissey, Audrey Mignet, Nathalie Fournier, Thierry Andrieux, Karine |
author_facet | Fliedel, Louise Alhareth, Khair Seguin, Johanne El-Khashab, Marwa Chissey, Audrey Mignet, Nathalie Fournier, Thierry Andrieux, Karine |
author_sort | Fliedel, Louise |
collection | PubMed |
description | Pregnant women are still considered as drug orphans. Developing new medications for pregnancy complications is an urgent need. Nanomedicines seem to be a promising approach to control the biodistribution of drugs to ensure both the mother’s and the fetus’ safety. Understanding the interaction between nanoparticles and the placental barrier is a key factor to the success of the development of nanomedicines for pregnant women. In this study, we evaluated the behavior of fluorescent PEGylated liposomes and lipoplexes in human placental tissue using in vitro and ex vivo models, BeWo cell culture and suspended villous placental explants, respectively. Fluorescent based analytical tools such as Fluorescence activated cells sorting (FACS), confocal microscopy and HPLC coupled to fluorescence detection were used to assess liposomes penetration and their endocytosis mechanisms in the placenta. First, no influence of the PEGylation density was observed on the cellular internalization of liposomal formulations using both models. The comparison between neutral and cationic liposomes exhibits a significant higher internalization of the cationic formulation compared to the neutral ones. In addition, the HPLC quantification of the fluorescent liposomes in human villous explants demonstrated an increase of cationic liposomes uptake with increasing incubation concentrations. Similar uptake of cationic liposomes and lipoplexes, containing the same cationic lipid, the DMAPAP but with an overall neutral surface charge, was observed and evidenced the higher effect of composition than charge surface on trophoblast penetration. Moreover, both cationic liposomes and lipoplexes exhibited an endocytosis mechanism of internalization via pathways implicating dynamin. These data highlight the key role of the liposome’s lipid composition and the possibility to modulate their internalization in the placenta by adjusting their design. |
format | Online Article Text |
id | pubmed-9181748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91817482022-06-10 Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta Fliedel, Louise Alhareth, Khair Seguin, Johanne El-Khashab, Marwa Chissey, Audrey Mignet, Nathalie Fournier, Thierry Andrieux, Karine Int J Mol Sci Article Pregnant women are still considered as drug orphans. Developing new medications for pregnancy complications is an urgent need. Nanomedicines seem to be a promising approach to control the biodistribution of drugs to ensure both the mother’s and the fetus’ safety. Understanding the interaction between nanoparticles and the placental barrier is a key factor to the success of the development of nanomedicines for pregnant women. In this study, we evaluated the behavior of fluorescent PEGylated liposomes and lipoplexes in human placental tissue using in vitro and ex vivo models, BeWo cell culture and suspended villous placental explants, respectively. Fluorescent based analytical tools such as Fluorescence activated cells sorting (FACS), confocal microscopy and HPLC coupled to fluorescence detection were used to assess liposomes penetration and their endocytosis mechanisms in the placenta. First, no influence of the PEGylation density was observed on the cellular internalization of liposomal formulations using both models. The comparison between neutral and cationic liposomes exhibits a significant higher internalization of the cationic formulation compared to the neutral ones. In addition, the HPLC quantification of the fluorescent liposomes in human villous explants demonstrated an increase of cationic liposomes uptake with increasing incubation concentrations. Similar uptake of cationic liposomes and lipoplexes, containing the same cationic lipid, the DMAPAP but with an overall neutral surface charge, was observed and evidenced the higher effect of composition than charge surface on trophoblast penetration. Moreover, both cationic liposomes and lipoplexes exhibited an endocytosis mechanism of internalization via pathways implicating dynamin. These data highlight the key role of the liposome’s lipid composition and the possibility to modulate their internalization in the placenta by adjusting their design. MDPI 2022-06-04 /pmc/articles/PMC9181748/ /pubmed/35682978 http://dx.doi.org/10.3390/ijms23116299 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fliedel, Louise Alhareth, Khair Seguin, Johanne El-Khashab, Marwa Chissey, Audrey Mignet, Nathalie Fournier, Thierry Andrieux, Karine Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta |
title | Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta |
title_full | Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta |
title_fullStr | Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta |
title_full_unstemmed | Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta |
title_short | Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta |
title_sort | influence of liposomes’ and lipoplexes’ physicochemical characteristics on their uptake rate and mechanisms by the placenta |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181748/ https://www.ncbi.nlm.nih.gov/pubmed/35682978 http://dx.doi.org/10.3390/ijms23116299 |
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