Within each system, CUR molecules can be seen establishing H-bonds to polymer carbonyl oxygens of the tertiary amides via their phenolic hydroxyl groups (Figure , 7B, 7C-II and 7D-III), sometimes including bridging water molecules (Figure -III and 7D-II). This conforms to previous NMR studies of A-pPrOzi-A systems and might result in an effective (yet transient) polymer cross-linking. In every system, about 90 % of such links established via directly double-H-bonded CUR molecules are formed intermolecularly between different chains. This could possibly impact solubility and colloidal stability when occurring in the corona, in particular between two individual micelles (not implemented in the present model). In accordance with this experimental study, the keto-enol moiety rarely establishes similar interactions. CUR-polymer H-bonding affecting overall hydrophilicity of delivery systems has also been discussed as an important factor for drug solubilization in recent modeling studies regarding (PEG-)chitosan-based DDS. Apart from these interactions, the lipophilic drug molecules are embedded within the mostly hydrophobic backbones and sidechains of the polymers. Within areas of high CUR concentrations, π-π stacking and CUR-CUR H-bonds (Figure -II) can be observed, with the carbonyl group of the keto-enol moiety also partly functioning as an acceptor. At high drug loadings, CUR molecules in the outer regions of the micelles do not diffuse into the bulk water but rather move around on, or stick to, the surface of the corona; as a result the latter becomes more hydrophobic. In vitro, such a situation would be expected to lead to micelle-micelle interactions, compromising colloidal stability. As noted before, when maximum LC is exceeded in vitro for the systems investigated here, it is not the drug that is precipitating, but the drug-loaded micelles form a gel phase of polymer and drug, in line with the hypothesis of physically cross-linked micelles. it could be postulated that, in an in vivo environment, such sticky patches possibly increase the strength of the interaction with either a cell membrane or a protein, e.g. serum albumin, affecting drug release, endocytosis and pharmacokinetics.