Ethosomal Nanocarriers for Trans-Resveratrol Delivery: Formulation, Physicochemical Characterization, Stability, and In Vitro Release Performance
Year: 2026
Type: article
Abstract: Background: Trans-resveratrol (3,5,4′-trihydroxystilbene) is a natural polyphenolic antioxidant widely used in anti-aging dermocosmetics for its strong radical-scavenging capacity and its activation of cell-protective pathways such as SIRT1. However, its poor aqueous solubility, photochemical lability, and low bioavailability limit its incorporation into topical formulations and its delivery into the skin. Objective: In this study, ethosomal nanocarriers were designed as a phospholipid–ethanol vesicular system to solubilize, stabilize, and control the release of trans-resveratrol for dermocosmetic applications. Microfluidization process is not a commonly used method, however under optimized pressure circulating the formulation through the interaction chamber can produce ethosomes with desirable colloidal stability as an easy method. Methods: Resveratrol-loaded ethosomes were prepared with synthetic phosphatidylcholine (Lipoid P75), ethanol, and vitamin E. Microfluidisation was used as an easy method which was optimized by varying the number of high-pressure homogenization cycles and the pressure applied. Vesicle size, size distribution and distribution uniformity, zeta potential, pH, conductivity, density, and long-term stability were monitored for up to 180 days; morphology was examined by cryo-SEM and molecular compatibility by FTIR. A trans-resveratrol HPLC assay was developed and validated according to ICH Q2guidelines for quantitative analysis. Encapsulation efficiency was determined by HPLC after ultracentrifugation, cytotoxicity was assessed in HaCaT keratinocytes, and in vitro release was evaluated using Franz diffusion cells with two different membranes. Results: All ethosome formulations yielded a nanoscale size distribution (median diameter around 190 nm) and good colloidal stability, with absolute zeta potentials above the 30 mV threshold at early time points and had skin-compatible pH (around 6.5). The optimized formulation (T16) achieved a high encapsulation efficiency (EE) of 95.5% on day 1, 84.2% EE was retained after 180 days, consistent with strong partitioning of the lipophilic active into the ethanol–phospholipid bilayer. FTIR confirmed preservation of the phospholipid bilayer and indicated non-covalent loading, with the resveratrol bands largely masked by the dominant lipid signals. Cryo-SEM confirmed near-spherical vesicles with narrow size distribution. In vitro release showed a sustained, controlled release profile relative to a 1.5% resveratrol solution. Slower diffusion across the skin-mimicking Strat-M membrane was observed compared to cellulose acetate membrane. Conclusions: Using Optimized trans-resveratrol-loaded ethosomes represent a stable, efficient ethosomes enabling formulation stability and controlled topical release. The antioxidant and photoprotective efficacy of the loaded system was not assessed in this study and is identified as a topic for future work.
Source: Pharmaceutics
Authors: Yasemin Yağan Uzuner, Hakan Sevinç
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funder: Yeditepe Üniversitesi
OpenAlex ID: W7204834334