Influence of Liposomes' and Lipoplexes' Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Liposomes*/chemistry ; Placenta*/metabolism; Cations/metabolism ; Female ; Humans ; Lipids/chemistry ; Pregnancy ; Tissue Distribution
    • Abstract:
      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.
    • References:
      Pharmaceutics. 2016 Dec 21;8(4):. (PMID: 28009829)
      Placenta. 2013 Dec;34(12):1216-22. (PMID: 24183755)
      Cell Commun Signal. 2015 Apr 10;13:24. (PMID: 25889964)
      Int J Nanomedicine. 2018 Jul 11;13:4073-4082. (PMID: 30034233)
      J Pharm Res Int. 2017;17(5):. (PMID: 29214230)
      Mol Biol Cell. 2004 Aug;15(8):3542-52. (PMID: 15146059)
      Pediatr Res. 1997 Oct;42(4):520-7. (PMID: 9380447)
      Nanoscale. 2019 Jun 27;11(25):12285-12295. (PMID: 31211316)
      J Vet Med Sci. 2014 Mar;76(3):377-87. (PMID: 24257253)
      J Control Release. 2011 Jun 30;152(3):393-401. (PMID: 21497175)
      Am J Obstet Gynecol. 2021 Jul;225(1):33-42. (PMID: 33887238)
      Drug Discov Today. 2018 May;23(5):1099-1107. (PMID: 29391261)
      Hum Reprod. 1997 Jun;12(6):1343-8. (PMID: 9222028)
      Nanomedicine (Lond). 2015 Jul;10(14):2229-47. (PMID: 26214358)
      AAPS J. 2011 Dec;13(4):585-97. (PMID: 21904966)
      Ther Deliv. 2017 Dec;8(12):1023-1025. (PMID: 29125062)
      Colloids Surf B Biointerfaces. 2017 Oct 1;158:93-101. (PMID: 28683347)
      Ochsner J. 2020 Spring;20(1):39-43. (PMID: 32284681)
      Adv Drug Deliv Rev. 2019 Mar 15;143:68-96. (PMID: 31022434)
      Nanomedicine. 2013 Feb;9(2):233-46. (PMID: 22698807)
      Mol Ther Methods Clin Dev. 2014 Dec 17;1:14058. (PMID: 26052524)
      Environ Toxicol. 2017 Jun;32(6):1742-1753. (PMID: 28181394)
      Int J Pharm. 2017 Nov 5;532(2):729-737. (PMID: 28757257)
      Int J Cancer. 2003 Jul 1;105(4):561-7. (PMID: 12712451)
      Int J Nanomedicine. 2011;6:3087-98. (PMID: 22163162)
      Nanomedicine (Lond). 2016 Apr;11(8):941-57. (PMID: 26979802)
      Int J Pharm. 2019 Aug 15;567:118479. (PMID: 31255777)
      Pharm Res. 2003 Jul;20(7):962-8. (PMID: 12880280)
      Molecules. 2018 May 04;23(5):. (PMID: 29734663)
      Bioconjug Chem. 2005 May-Jun;16(3):608-14. (PMID: 15898728)
      J Pharm Pharmacol. 1997 Jul;49(7):675-81. (PMID: 9255710)
      Sci Rep. 2018 Feb 28;8(1):3748. (PMID: 29491352)
      Toxicol Lett. 2015 Dec 3;239(2):108-14. (PMID: 26383631)
      J Gene Med. 2010 Jan;12(1):45-54. (PMID: 19937995)
    • Contributed Indexing:
      Keywords: cellular uptake; endocytosis; ex vivo model; lipoplexes; liposomes; placental explants
    • Accession Number:
      0 (Cations)
      0 (Lipids)
      0 (Liposomes)
    • Publication Date:
      Date Created: 20220610 Date Completed: 20220613 Latest Revision: 20220716
    • Publication Date:
      20240105
    • Accession Number:
      PMC9181748
    • Accession Number:
      10.3390/ijms23116299
    • Accession Number:
      35682978