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 (<b>H</b>) and cetyltrimethylammonium bromide (CTAB) using a microemulsion method. Dynamic light scattering revealed that the resulting CTAB/<b>H</b> 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 spectroscopy, 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 (<b>Q</b>). The CTAB/<b>H</b> system displayed low cytotoxicity (up to 50 µg/mL) and pronounced antioxidant activity, as evidenced by DPPH, ABTS, and FRAP assays. Quercetin-loaded nanoparticles (CTAB/<b>H</b>/<b>Q</b>) enhanced cellular uptake and exhibited a marked cytoprotective effect against H₂O₂-induced oxidative stress in NIH-3T3 fibroblasts.