Low molecular weight poly (2-dimethylamino ethylmethacrylate) polymers with controlled.positioned fluorescent labeling: Synthesis, characterization and in vitro interaction with human endothelial cells

Luca Flebus, Francois Lombart, Chantal Sevrin, Jean-Olivier Defraigne, Pierre Peters, Ladan Parhamifar, Daniel G. M. Molin, Christian Grandfils*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)

Abstract

Poly (2-dimethylamino ethylmethacrylate) (PDMAEMA) is an attractive non-degradable polymer studied as nonviral vector for gene delivery but it can be also adopted for delivery of other biopharmaceutical drugs. As a parenteral carrier, the PDMAEMA free form (FF) might interact with tissues and cells. Few data are available on its selective internalization and efflux from cells, while the majority of studies published have followed the distribution of DNA complexed with PDMAEMA. In order to address polycation safety, the first aim was to synthesize by atom transfer radical polymerisation (ATRP) fluorescent labeled PDMAEMA of low molecular weight (Mw) (below 15 kDa), controlling the position and density of fluorescein. The second goal was to analyze the possible difference in uptake and subcellular distribution of this labeled FF polycation between human umbilical vein endothelial cells (HUVEC) and hCMEC/D3 cells. These two cell lines have been chosen in order to detect selectivity towards the blood-brain barrier (BBB). In both cases, polycation was detected along the plasma membrane followed by progressive migration to the pen-nuclear region, where it overlapped with lysosomal structures. The analysis by fluorescence-activated cell sorting (FACS) of the PDMAEMA uptake by hCMEC/D3 cells showed a significant (p
Original languageEnglish
Pages (from-to)278-287
JournalInternational Journal of Pharmaceutics
Volume478
Issue number1
DOIs
Publication statusPublished - 15 Jan 2015

Keywords

  • Functional polymers
  • Polycations
  • Poly(2-dimethylamino-ethylmethacrylate)
  • Biomedical applications
  • Cell trafficking

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