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

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.

Reaching High Stereoselectivity and Activity in Organocatalyzed Ring-Opening Polymerization of Racemic Lactide by the Combined Use of a Chiral (Thio)Urea and a N-Heterocyclic Carbene

“…In this context, organic catalysts have emerged as attractive alternatives for the stereoselective ROP of rac -LA . Some organic catalysts, such as certain phosphazenes, have been found to be toxic. , Despite the emergence and development of asymmetric organic catalysis in molecular chemistry, which was crowned in 2021 with the award of the Nobel Prize in Chemistry to McMillan and List, − adaptation of this concept in polymer synthesis, that is, stereoselective polymerization employing chiral organic catalysts, remains overlooked. Most of all, organic catalysts that would combine high stereoselectivity and catalytic activity, and operating at room temperature or above, are rare. − …”