# Physicochemical and Computational Study of the Encapsulation of Resv-4′-LA and Resv-4′-DHA Lipophenols by Natural and HP-β-CDs

## TL;DR

This study explores how two resveratrol-based compounds form micelles and interact with cyclodextrins, showing potential for drug delivery and food applications.

## Contribution

The study introduces novel resveratrol-based lipophenols and evaluates their encapsulation behavior with HP-β-CDs using physicochemical and computational methods.

## Key findings

- LipoResv compounds have lower CMC values than free fatty acids, indicating higher hydrophobicity.
- Resv-4′-LA forms 1:1 complexes with HP-β-CDs, while Resv-4′-DHA forms 1:2 complexes with lower affinity.
- Environmental factors like pH and temperature significantly affect CMC and binding constants.

## Abstract

This study investigates the self-assembly and host–guest complexation behaviour of novel resveratrol-based lipophenols (LipoResv)—resveratrol-4′-linoleate (Resv-4′-LA) and resveratrol-4′-docosahexaenoate (Resv-4′-DHA)—with hydroxypropyl-β-cyclodextrins (HP-β-CDs). These amphiphilic molecules display surfactant-like properties, forming micellar aggregates in aqueous media. Fluorescence spectroscopy was used to determine the critical micelle concentration (CMC), revealing that LipoResv exhibit significantly lower CMC values than their free fatty acids, indicating higher hydrophobicity. The formation of inclusion complexes with HP-β-CDs was evaluated based on changes in CMC values and further confirmed by dynamic light scattering (DLS) and molecular modelling analyses. Resv-4′-LA formed 1:1 complexes (Kc = 720 M−1), while Resv-4′-DHA demonstrated a 1:2 stoichiometry with lower affinity constants (K1 = 17 M−1, K2 = 0.18 M−1). Environmental parameters (pH, temperature, and ionic strength) significantly modulated CMC and binding constants. Computational docking and molecular dynamics simulations supported the experimental findings by revealing the key structural determinants of the host–guest affinity and micelle stabilization. Ligand efficiency (LE) analysis further aligned with the experimental data, favouring the unmodified fatty acids. These results highlight the versatile encapsulation capacity of HP-β-CDs for bioactive amphiphile molecules and support their potential applications in drug delivery and functional food systems.