Self-Assembly behavior of amphiphilic janus dendrimers in water: a combined experimental and coarse-grained molecular dynamics simulation approach

Amphiphilic Janus dendrimers (JDs) are repetitively branched molecules with\ua0hydrophilic and hydrophobic components that self-assemble in water to form a variety of\ua0morphologies, including vesicles analogous to liposomes with potential pharmaceutical\ua0and medical application. To date, the self-assembly of JDs has not been fully\ua0investigated thus it is important to gain insight into its mechanism and dependence on\ua0JDs’ molecular structure. In this study, a series of amphiphilic JDs with variations in their\ua0core and branching pattern was synthesized and its aggregation behavior in water was\ua0evaluated using experimental and computational methods. JDs were obtained from 2,2-bis(hydroxymethyl)propionic acid, myristic acid and different glycols. Dispersions of JDs\ua0in water were carried out using the thin-film hydration, solvent injection methods and by\ua0microfluidics, using double emulsion drops with ultrathin shells as templates.\ua0Furthermore, a coarse-grained molecular dynamics (CG-MD) simulation was performed\ua0to study the mechanism of JDs aggregation. The resulting assemblies were\ua0characterized by optical microscopy, dynamic light scattering, confocal microscopy, and\ua0atomic force microscopy. The obtaining of assemblies in water with no interdigitated\ua0bilayers was confirmed by the experimental characterization and CG-MD simulation for\ua0one of the dendrimers. Assemblies with dendrimersome characteristics were obtained\ua0using the solvent injection method. Also,\ua0monodisperse nanometric assemblies were\ua0obtained by this method. The use of microfluidics enables the production of giant\ua0dendrimersomes from highly hydrophobic JDs, even when the dendrimers did not form\ua0vesicles using the thin-film hydration method. The results of this study establish a\ua0relationship between the molecular structure of the JDs and the properties of its\ua0aggregates in water. These results could be relevant for the design of novel JDs with\ua0tailored assemblies suitable for drug delivery systems. In addition, this study offers an\ua0approach to produce dendrimersomes in a more controlled way