Synthesis of Poly(Dimethylmalic Acid) Homo- and Copolymers to Produce Biodegradable Nanoparticles for Drug Delivery: Cell Uptake and Biocompatibility Evaluation in Human Heparg Hepatoma Cells

Ali Khalil; Saad Saba; Catherine Ribault; Manuel Vlach; Pascal Loyer; Olivier Coulembier; Sandrine Cammas-Marion

doi:10.3390/polym12081705

Synthesis of Poly(Dimethylmalic Acid) Homo- and Copolymers to Produce Biodegradable Nanoparticles for Drug Delivery: Cell Uptake and Biocompatibility Evaluation in Human Heparg Hepatoma Cells

Polymers (Basel). 2020 Jul 29;12(8):1705. doi: 10.3390/polym12081705.

Authors

Ali Khalil^{1

2}, Saad Saba³, Catherine Ribault³, Manuel Vlach³, Pascal Loyer³, Olivier Coulembier¹, Sandrine Cammas-Marion^{2

3}

Affiliations

¹ Laboratory of Polymeric and Composite Materials, Center of Innovation and Research in Materials and Polymers (CIRMAP), University of Mons (UMons), Place du Parc 23, 7000 Mons, Belgium.
² ENSCR, CNRS, ISCR (Institut des Sciences Chimiques de Rennes) - UMR 6226, Univ Rennes, 35000 Rennes, France.
³ INSERM, INRAE, Univ Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, France.

Abstract

Hydrophobic and amphiphilic derivatives of the biocompatible and biodegradable poly(dimethylmalic acid) (PdiMeMLA), varying by the nature of the lateral chains and the length of each block, respectively, have been synthesized by anionic ring-opening polymerization (aROP) of the corresponding monomers using an initiator/base system, which allowed for very good control over the (co)polymers' characteristics (molar masses, dispersity, nature of end-chains). Hydrophobic and core-shell nanoparticles (NPs) were then prepared by nanoprecipitation of hydrophobic homopolymers and amphiphilic block copolymers, respectively. Negatively charged NPs, showing hydrodynamic diameters (Dh) between 50 and 130 nm and narrow size distributions (0.08 < PDI < 0.22) depending on the (co)polymers nature, were obtained and characterized by dynamic light scattering (DLS), zetametry, and transmission electron microscopy (TEM). Finally, the cytotoxicity and cellular uptake of the obtained NPs were evaluated in vitro using the hepatoma HepaRG cell line. Our results showed that both cytotoxicity and cellular uptake were influenced by the nature of the (co)polymer constituting the NPs.

Keywords: HepaRG cells; cellular uptake; in vitro cytotoxicity; poly(dimethylmalic acid) derivatives; polymeric nanoparticles.