# Spontaneous Emulsification as a Low-Energy Strategy for Designing and Optimizing Resveratrol-Loaded Nanostructured Lipid Carriers

**Authors:** Nicoly T. R. Britto, Lilian R. S. Montanheri, Juliane N. B. D. Pelin, Tereza S. Martins, Patrícia S. Lopes, Vânia R. Leite-Silva, Newton Andreo-Filho

PMC · DOI: 10.1021/acsomega.5c10613 · ACS Omega · 2026-02-11

## TL;DR

This paper introduces a low-energy method to create stable nanostructured lipid carriers for delivering resveratrol, a bioactive compound, with high efficiency and long-term stability.

## Contribution

The novel contribution is the use of spontaneous emulsification to produce resveratrol-loaded NLCs without organic solvents, offering a sustainable alternative to high-energy methods.

## Key findings

- Resveratrol-loaded NLCs achieved 99% encapsulation efficiency with a mean particle size of 90 nm.
- The system showed colloidal stability for 90 days at 8 °C and sustained release of resveratrol.
- Characterization confirmed successful incorporation of resveratrol into the nanocarriers.

## Abstract

Nanostructured lipid carriers (NLCs) have proven to be
effective
for the delivery of lipophilic drugs by combining high encapsulation
capacity with controlled release properties. In this study, NLCs were
developed using spontaneous emulsification, a low-energy, simple method
that is free of organic solvents. Cetearyl alcohol and Kolliphor RH
40 were employed as the solid lipid and surfactant, respectively.
The formulation and process were optimized through a Box–Behnken
design, considering mean particle size and size uniformity, as determined
by laser diffraction. Colloidal stability was improved by the addition
of sodium lauryl sulfate and adjustments to the dispersion polymer.
Resveratrol (RVL), used as a model bioactive compound, achieved an
encapsulation efficiency of 99%, with a mean particle size of 90 nm,
a polydispersity index of 0.2, and a zeta potential of −37
mV, remaining stable for 90 days at 8 °C. Characterization by
differential scanning calorimetry/thermogravimetry, Fourier transform
infrared, and transmission electron microscopy confirmed the incorporation
of the active compound as well as the composition and morphology of
the nanocarriers. The system exhibited a delayed and sustained release
of RVL, highlighting its potential as a platform for the delivery
of bioactive compounds. Overall, the results demonstrate that spontaneous
emulsification is a viable and sustainable alternative to the high-energy
methods predominantly reported in the literature, enabling the production
of stable and efficient NLCs for pharmaceutical and cosmetic applications.

## Linked entities

- **Chemicals:** resveratrol (PubChem CID 5056), Cetearyl alcohol (PubChem CID 62238), sodium lauryl sulfate (PubChem CID 3423265)

## Full-text entities

- **Genes:** EYS (EGF-like photoreceptor maintenance factor) [NCBI Gene 346007] {aka C6orf178, C6orf179, C6orf180, EGFL10, EGFL11, RP25}, SMG1 (SMG1 nonsense mediated mRNA decay associated PI3K related kinase) [NCBI Gene 23049] {aka 61E3.4, ATX, LIP}, CCT [NCBI Gene 907], PADI1 (peptidyl arginine deiminase 1) [NCBI Gene 29943] {aka HPAD10, PAD1, PDI, PDI1}
- **Diseases:** SLS (MESH:C562576), NLC-RVL (MESH:D011017), PSD (MESH:D020243)
- **Chemicals:** phosphotungstic acid (MESH:D010772), cetrimonium chloride (MESH:D000077286), Na2SO4 (MESH:C012036), Cetostearyl alcohol (MESH:C010405), oil (MESH:D009821), PEG-40 (MESH:C000595210), Na2HPO412H2O (-), aluminum (MESH:D000535), Disodium phosphate dodecahydrate (MESH:C018279), P188 (MESH:D020442), alcohol (MESH:D000438), GS (MESH:C048159), CA (MESH:C419308), Tw (MESH:D011136), ether (MESH:D004986), fexofenadine (MESH:C093230), polystyrene (MESH:D011137), Caprylic/Capric Triglyceride (MESH:C000709826), Lipid (MESH:D008055), CTAC (MESH:C018375), N (MESH:D009584), C (MESH:D002244), polymer (MESH:D011108), platinum (MESH:D010984), PTFE (MESH:D011138), SLS (MESH:D012967), Polyvinylpyrrolidone (MESH:D011205), RVL (MESH:D000077185), hydroxyl (MESH:D017665), EtOH (MESH:D000431), water (MESH:D014867), DTG (MESH:C562325), C20 (MESH:D002592)
- **Cell lines:** NLC-RVL — Homo sapiens (Human), Hybridoma (CVCL_9089)

## Full text

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## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12947224/full.md

## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12947224/full.md

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Source: https://tomesphere.com/paper/PMC12947224