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Int J Pharm. 2016 Nov 20;513(1-2):438-452. doi: 10.1016/j.ijpharm.2016.09.048. Epub 2016 Sep 15.

Opsonisation of nanoparticles prepared from poly(β-hydroxybutyrate) and poly(trimethylene carbonate)-b-poly(malic acid) amphiphilic diblock copolymers: Impact on the in vitro cell uptake by primary human macrophages and HepaRG hepatoma cells.

Author information

1
INSERM UMR S-991, Foie, Métabolismes et Cancer; Université de Rennes 1; CHU Pontchaillou Rennes, 35033 Rennes, France.
2
Institut des Sciences Chimiques de Rennes; UMR 6226 CNRS; Université de Rennes 1, Campus de Beaulieu, 263 Avenue du Général Leclerc, F-35042 Rennes Cedex, France.
3
Ecole Nationale Supérieure de Chimie de Rennes, Institute des Sciences Chimiques de Rennes, Université de Rennes 1, 11 allée de Beaulieu, CS 50837, 35708 Rennes Cedex 7, France.
4
INSERM UMR S-991, Foie, Métabolismes et Cancer; Université de Rennes 1; CHU Pontchaillou Rennes, 35033 Rennes, France. Electronic address: pascal.loyer@univ-rennes1.fr.

Abstract

The present work reports the investigation of the biocompatibility, opsonisation and cell uptake by human primary macrophages and HepaRG cells of nanoparticles (NPs) formulated from poly(β-malic acid)-b-poly(β-hydroxybutyrate) (PMLA-b-PHB) and poly(β-malic acid)-b-poly(trimethylene carbonate) (PMLA-b-PTMC) diblock copolymers, namely PMLA800-b-PHB7300, PMLA4500-b-PHB4400, PMLA2500-b-PTMC2800 and PMLA4300-b-PTMC1400. NPs derived from PMLA-b-PHB and PMLA-b-PTMC do not trigger lactate dehydrogenase release and do not activate the secretion of pro-inflammatory cytokines demonstrating the excellent biocompatibility of these copolymers derived nano-objects. Using a protein adsorption assay, we demonstrate that the binding of plasma proteins is very low for PMLA-b-PHB-based nano-objects, and higher for those prepared from PMLA-b-PTMC copolymers. Moreover, a more efficient uptake by macrophages and HepaRG cells is observed for NPs formulated from PMLA-b-PHB copolymers compared to that of PMLA-b-PTMC-based NPs. Interestingly, the uptake in HepaRG cells of NPs formulated from PMLA800-b-PHB7300 is much higher than that of NPs based on PMLA4500-b-PHB4400. In addition, the cell internalization of PMLA800-b-PHB7300 based-NPs, probably through endocytosis, is strongly increased by serum pre-coating in HepaRG cells but not in macrophages. Together, these data strongly suggest that the binding of a specific subset of plasmatic proteins onto the PMLA800-b-PHB7300-based NPs favors the HepaRG cell uptake while reducing that of macrophages.

KEYWORDS:

HepaRG cells; Macrophages; Nanoparticle; Poly(hydroxy alkanoate); Poly(malic acid); Poly(trimethylene carbonate)

PMID:
27640247
DOI:
10.1016/j.ijpharm.2016.09.048
[Indexed for MEDLINE]
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