Water-Dispersible Supramolecular Nanoparticles Formed by Dicarboxyl-bis-pillar[5]arene/CTAB Host–Guest Interaction as an Efficient Delivery System of Quercetin

Supramolecular nanoparticles offer an efficient strategy to enhance the solubility, stability,
and bioavailability of poorly water-soluble therapeutic molecules. In this study, water-
dispersible SNPs were successfully prepared from dicarboxyl-bis-pillar[5]arene (H) and
cetyltrimethylammonium bromide (CTAB) using a microemulsion method. Dynamic light
scattering revealed that the resulting CTAB/H nanoparticles possessed a size distribution
centered around 40 nm, a positive surface charge (+15 mV), and exhibited high colloidal
stability over three months. 1H NMR, 2D TOCSY, 2D NOESY, diffusion ordered NMR spec-
troscopy, and UV-Vis investigations confirmed the inclusion of the CTAB alkyl chain within
the pillar[5]arene cavity, supporting the formation of stable supramolecular assemblies
capable of efficiently encapsulating the poorly water-soluble flavonol quercetin (Q). The
CTAB/H system displayed low cytotoxicity (up to 50 µg/mL) and pronounced antioxidant
activity, as evidenced by DPPH, ABTS, and FRAP assays. Quercetin-loaded nanoparti-
cles (CTAB/H/Q) enhanced cellular uptake and exhibited a marked cytoprotective effect
against H2O2-induced oxidative stress in NIH-3T3 fibroblasts.