Supramolecular engineering of micellar systems: Precision control on self-assembly, polarity, and charge for enhanced nanocarrier design

In the quest for enhanced drug delivery systems, the combination of supramolecular receptors and surfactants represents a promising step toward developing innovative and highly efficient nanocarriers. This research highlights the paramount advantages of synergizing these elements, focusing on the manipulation of the selfassembly, charge, and polarity of the hybrid nanostructures resulting from merging these building blocks. In this vein, this work reveals that the integration of hexamethylated p-sulfonatocalix[6]arene (SC6A) and dodecyltrimethylammonium bromide (DTAB) offers significant advantages over those colloidal nanostructures stemming from the use of surfactant alone. These include the ability to stimulate early self-assembly, thereby facilitating the formation of stable nanocarriers, even in high-dilution scenarios. Additionally, the electrostatic balance established within the macrocycle-surfactant host-guest complexes can be harnessed to finely adjust the charge of the hydrophilic micellar corona. This holds great promise for modulating the bio-interaction capabilities of nanocarriers. Furthermore, the inclusion of the macrocycle in the colloidal structure induces significant alterations in the arrangement of low-molecular-weight surfactants. This leads to a significant transformation in the hydrophobic properties of the micellar core, which can be exploited to tailor this microenvironment to match the lipophilicity of specific drugs. In this regard, our findings reveal that while conventional DTAB micelles generally replicate the polarity of a solvent with a dielectric constant of 37.7, engineered SC6A-DTAB aggregates demonstrate a capability to reach a polarity akin to a solvent with dielectric constant of 17.5. This spectrum of hydrophobicities within the micellar core represents a significant advancement and opens up new possibilities for drug delivery applications.