Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release

Yasemin Yağan Uzuner; Bilge Demirci

doi:10.17776/csj.2012359

Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release

Abstract

Combining retinol and vitamin C (Vit C) in one topical formulation is challenging: retinol is lipophilic and easily oxidised, whereas Vit C is hydrophilic, and both are chemically unstable. This study aimed to co-encapsulate retinol and a stable Vit C derivative, 3-O-ethyl ascorbic acid, in ethosomes produced by high-pressure microfluidization. The ethosomes were characterised by particle size, polydispersity index, zeta potential, pH and transmission electron microscopy, and their physical stability was followed for 60 days at 2–8 °C, 25 °C, 30 °C and 40 °C. In vitro release through a cellulose acetate membrane and permeation across the synthetic skin-mimetic Strat-M® membrane were studied in Franz diffusion cells and compared with a solution and a conventional gel. The loaded ethosomes were spherical, with sizes of approximately 140–160 nm that remained essentially unchanged for 60 days at 2–8 °C, whereas samples stored at 30 °C and 40 °C had markedly larger vesicles; refrigerated storage is required. Encapsulation efficiency was 98.9% for retinol and 33.1% for Vit C. Expressed as a percentage of the applied dose, the cumulative amounts of both actives released or permeated from the ethosomal product over 2 h were significantly lower than those from the solution and the gel (28–50% of the solution values at 120 min; p < 0.001). Microfluidization is a simple and suitable method for producing ethosomes that co-encapsulate hydrophilic and lipophilic anti-ageing actives with a release-retarding effect. Because synthetic membranes were used, ex vivo and in vivo studies are needed to confirm skin delivery.

Keywords

Anti-ageing, Ethosomes, Microfluidization, Retinol, Vit C

Supporting Institution

Acibadem Mehmet Ali Aydinlar University, Faculty of Pharmacy

Project Number

(ABAPKO) FAST SUPPORT program (2022/02-17).

Ethical Statement

This study did not involve invasive procedures on humans or animals; therefore, ethics committee approval was not required.

Thanks

We would like to thank Acıbadem University Faculty of Pharmacy and all other departments for allowing us to use the necessary equipment and supplies, and our colleagues for their collaborations. We also thank Acıbadem University Scientific Projects Coordination Unit (ABAPKO) for supporting this project under FAST SUPPORT program (2022/02 -17).

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Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Yasemin Yağan Uzuner ^*
0000-0001-6586-4158
Türkiye

Bilge Demirci
0009-0009-5787-2970
Türkiye

Publication Date

October 27, 2026

Submission Date

August 6, 2026

Acceptance Date

October 15, 2026

Published in Issue

Year 2026 Volume: 47 Number: 5

DOI

https://doi.org/10.17776/csj.2012359

IZ

https://izlik.org/JA76CX47YD

APA

Yağan Uzuner, Y., & Demirci, B. (2026). Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release. Cumhuriyet Science Journal, 47(5), 961-972. https://doi.org/10.17776/csj.2012359

AMA

1.Yağan Uzuner Y, Demirci B. Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release. CSJ. 2026;47(5):961-972. doi:10.17776/csj.2012359

Chicago

Yağan Uzuner, Yasemin, and Bilge Demirci. 2026. “Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release”. Cumhuriyet Science Journal 47 (5): 961-72. https://doi.org/10.17776/csj.2012359.

EndNote

Yağan Uzuner Y, Demirci B (October 1, 2026) Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release. Cumhuriyet Science Journal 47 5 961–972.

IEEE

[1]Y. Yağan Uzuner and B. Demirci, “Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release”, CSJ, vol. 47, no. 5, pp. 961–972, Oct. 2026, doi: 10.17776/csj.2012359.

ISNAD

Yağan Uzuner, Yasemin - Demirci, Bilge. “Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release”. Cumhuriyet Science Journal 47/5 (October 1, 2026): 961-972. https://doi.org/10.17776/csj.2012359.

JAMA

1.Yağan Uzuner Y, Demirci B. Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release. CSJ. 2026;47:961–972.

MLA

Yağan Uzuner, Yasemin, and Bilge Demirci. “Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release”. Cumhuriyet Science Journal, vol. 47, no. 5, Oct. 2026, pp. 961-72, doi:10.17776/csj.2012359.

Vancouver

1.Yasemin Yağan Uzuner, Bilge Demirci. Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release. CSJ. 2026 Oct. 1;47(5):961-72. doi:10.17776/csj.2012359

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Co-Encapsulation of Retinol and 3-O-Ethyl Ascorbic Acid in Dual-Loaded Ethosomes Produced by High-Pressure Microfluidization: Characterization, Stability and In Vitro Release

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