# Unveiling Supramolecular Structures Formed by Menthol and Xanthan Gum in Oleic Acid-Based Microemulsions

## TL;DR

This study explores how menthol and xanthan gum affect the structure and properties of microemulsions for drug delivery.

## Contribution

The study reveals how menthol and xanthan gum modify microemulsion structures and physical properties for drug delivery.

## Key findings

- Menthol addition modulates droplet size, indicating drug entrapment in the oil phase.
- XG creates a 'pearl-necklace' structure without changing droplet size significantly.
- Rheology and texture analysis reveal property changes not detected by light scattering techniques.

## Abstract

Microemulsions (MEs) are delivery systems that can enhance
the
rate of drug dissolution due to their supramolecular structure. However,
adding drugs, such as menthol, and thickness agents, like xanthan
gum (XG), can significantly modify these nanoscaled architectures.
This study aimed to understand the mechanistic basis of supramolecular
structural modifications in oleic acid-based MEs induced by XG and
menthol addition. A multitechnique approach combining electron microscopy,
dynamic light scattering (DLS), small-angle X-ray scattering (SAXS),
rheology, and texture analysis was employed to characterize formulations
containing concentration ranges of menthol (0.1–1.0%w/w) and
XG (0.1–0.5%w/w). This complementary analytical strategy enabled
the detection of structural changes across different length scales.
Our findings revealed that menthol addition leads to droplet diameter
modulation (DLS: 127–157 nm; SAXS: 108–136 nm), suggesting
drug entrapment within the oil phase. XG addition produces a distinctive
interconnected “pearl-necklace” supramolecular architecture
without significant droplet size changes (DLS: 102–111 nm;
SAXS: 102 nm). Crucially, rheological and textural analyses detected
physical property modifications not identified by light scattering
techniques, with XG dramatically influencing consistency, firmness,
and adhesiveness, while menthol enhanced adhesive properties. These
structure–function correlations showed that rational ME design
can be achieved through controlled excipient addition. Collectively,
the nanoscaled pearl-necklace architecture and enhanced adhesive properties
suggest promising applications for sustained topical drug delivery,
warranting future investigation of skin permeation kinetics and therapeutic
efficacy in dermatological formulations.