In recent years, zwitterionic macromolecules have gained considerable interest in the biomedical field [1] as materials, which shield surfaces from unwanted interactions with the biological environment [2]. Along the polymer chain, zwitterionic macromolecules are comprised of monomers carrying both positive and negative functional groups, resulting in pronounced hydrophilicity while maintaining an overall neutral net charge. Thus, zwitterionic polymers are often well-solvated and their chemistry makes the attached chains protrude away from a surface to form brush-like (protecting) layers [3]. Polymer coatings with favorable properties for biomedical applications, such as enhanced anti-fouling behavior or the ability to elude the immune system, can be found in the group of poly(sulfobetaine)s, poly(carboxybetaine)s and poly(phosphorylcholine)s [4], [5], [6]. Among them, macromolecules based on bioinspired 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) have attracted attention due to their protein-repellent properties [7] and proven biocompatibility (in in vitro cell culture and in vivo including trials in humans) [8], [9].

Nanomedicine would especially profit from said highly hydrophilic, biocompatible coatings, as the smallest size of bare drug delivery vehicles often imposes challenges in terms of colloidal stability. A common strategy to decorate (hydrophobic) surfaces with steric stabilizers is to design amphiphilic (tri)block copolymers, which can be “attached” to the surface during or post manufacturing [10]. This approach is of particular interest for colloidal drug delivery systems, as it allows for “control” over the formed layer architecture (e.g., thickness and density of surface coverage) accompanied by a rather “simple” analytical characterization. Nevertheless, despite ongoing research, there is currently a lack of systematic studies addressing questions related to structure-function relationships of protecting coating layer architectures on colloidal drug delivery systems based on poly(phosphorylcholine)s [10], [11].

To close this gap, this study aimed at identifying general design principles and structure-function relationships of promising PMPC-based coating polymers in the context of optimizing the performance of colloidal drug delivery vehicles. A library of poly(MPC)-block-poly(propylene glycol)-block-poly(MPC) (PMPC-b-PPG-b-PMPC) triblock copolymers was synthesized and characterized systematically in terms of physicochemical properties, aqueous solubility, surface activity and in vitro cytotoxicity. Next, polymer nanoparticles were coated with the triblock copolymers and analyzed in detail for the structure of the formed PMPC layer and, furthermore, for its beneficial effect on colloidal stability and protein adsorption. The current results highlight how molecular weight and triblock copolymer composition govern the coating architecture, which is shown to be critical to the behavior of colloidal drug delivery vehicles under application of PMPC-b-PPG-b-PMPCs.