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

**Authors:** Marco Milone, Martina Mazzaferro, Antonella Calderaro, Giuseppe T. Patanè, Davide Barreca, Salvatore Patanè, Norberto Micali, Valentina Villari, Anna Notti, Melchiorre F. Parisi, Ilenia Pisagatti, Giuseppe Gattuso

PMC · DOI: 10.3390/ijms27010516 · International Journal of Molecular Sciences · 2026-01-04

## TL;DR

Researchers created water-dispersible nanoparticles to efficiently deliver quercetin, a poorly water-soluble compound, improving its stability and bioavailability.

## Contribution

A novel supramolecular nanoparticle system using dicarboxyl-bis-pillar[5]arene and CTAB for efficient quercetin delivery is introduced.

## Key findings

- The CTAB/H nanoparticles had a size of ~40 nm, positive charge, and high colloidal stability for three months.
- The system efficiently encapsulated quercetin and showed low cytotoxicity with strong antioxidant activity.
- Quercetin-loaded nanoparticles improved cellular uptake and provided cytoprotection against oxidative stress.

## Abstract

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 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 (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 nanoparticles (CTAB/H/Q) enhanced cellular uptake and exhibited a marked cytoprotective effect against H2O2-induced oxidative stress in NIH-3T3 fibroblasts.

## Linked entities

- **Chemicals:** quercetin (PubChem CID 5280343), cetyltrimethylammonium bromide (PubChem CID 5974), H2O2 (PubChem CID 784)

## Full-text entities

- **Diseases:** cytotoxicity (MESH:D064420)
- **Chemicals:** Quercetin (MESH:D011794), H (MESH:D006859), H2O2 (MESH:D006861), CTAB (MESH:D000077286), 1H (-), flavonol (MESH:C041477), Water (MESH:D014867), DPPH (MESH:C004931), Q (MESH:D005973), ABTS (MESH:C002502)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12786710/full.md

## References

74 references — full list in the complete paper: https://tomesphere.com/paper/PMC12786710/full.md

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Source: https://tomesphere.com/paper/PMC12786710