Improved ocular delivery of quercetin and resveratrol: A comparative study between binary and ternary cyclodextrin...

Area of Science:

• Ophthalmology
• Pharmaceutics
• Materials Science

Background:

• Dry Eye Disease (DED) prevalence is increasing globally, necessitating advanced therapeutic strategies.
• Polyphenols like quercetin (QUE) and resveratrol (RSV) possess antioxidant and anti-inflammatory properties beneficial for DED.
• Topical application of QUE and RSV is limited by poor aqueous solubility and chemical instability.

Purpose of the Study:

• To compare binary complexes of QUE/RSV with cyclodextrins (CD) and tertiary complexes including hyaluronic acid (HA).
• To evaluate the impact of these complexes on the solubility, stability, and efficacy of QUE and RSV for potential DED treatment.

Main Methods:

• Formation and characterization of binary (QUE/RSV-CD) and tertiary (QUE/RSV-CD-HA) complexes.
• Assessment of solubility and stability enhancement.
• Analysis of nanoaggregate formation using Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS).
• In vitro cytotoxicity testing on corneal (HCE) and conjunctival (IM-ConjEpi) cell lines.
• Evaluation of intracellular reactive oxygen species (ROS) scavenging activity.

Main Results:

• Both binary and tertiary complexes significantly improved QUE and RSV solubility and stability.
• Tertiary complexes formed spherical nanoaggregates with mean diameters of 103 nm (QUE) and 82 nm (RSV).
• No cytotoxic effects were observed in HCE and IM-ConjEpi cell lines for either complex type.
• Complexes effectively scavenged over 95% of intracellular ROS in both cell lines, with sustained antioxidant effect in HA-containing complexes.

Conclusions:

• Cyclodextrin complexation, particularly with hyaluronic acid, enhances the physicochemical properties of quercetin and resveratrol.
• The developed nanoformulations are non-cytotoxic and exhibit potent antioxidant activity, suitable for ocular application.
• These findings support the potential of QUE/RSV-CD-HA complexes as effective topical treatments for Dry Eye Disease.