Development, characterization of naringenin-loaded promising microemulsion formulations, and demonstration of anti-aging efficacy by in vitro enzyme activity and gene expression

Şahin D., Çağlar E. Ş., Boran T., Karadağ A. E., Özhan G., Üstündağ Okur N.

Journal of Drug Delivery Science and Technology, vol.84, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 84
  • Publication Date: 2023
  • Doi Number: 10.1016/j.jddst.2023.104422
  • Journal Name: Journal of Drug Delivery Science and Technology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, EMBASE
  • Keywords: Naringenin, Microemulsion, Antiaging, Anti-elastase, Gene expressions, Cell culture
  • Istanbul Medipol University Affiliated: Yes


This study aims to produce microemulsion formulations containing naringenin for anti-aging reasons. For this purpose, formulations of topical microemulsions including different cosurfactants and surfactants were developed, and a triangle phase diagram was utilized to determine the optimal microemulsion system. On the developed microemulsion formulations, characterization studies were performed. Ex vivo permeation-penetrating and in vitro release experiments were conducted. Anti-elastase, anti-collagenase, anti-tyrosinase, and antioxidant properties of the formulations were also evaluated. Experiments were conducted on cytotoxicity, cellular ROS, gene expression levels of oxidative stress-related genes, and cell culture. Droplet size, polydispersity index, zeta potential, pH, viscosity, turbidity of naringenin loaded formulations were found between 0.9147 ± 0.0316 and 1.938 ± 0.085 nm, 0.373 ± 0.025 and 0.410 ± 0.019, −0.0517 ± 0.0138 and −0.0990 ± 0.0110 mV, 5.110 ± 0.006 and 5.530 ± 0.006, 163.33 ± 5.77 and 450.00 ± 0.00 cP, 5.723 ± 0.068 and 9.323 ± 0.264 NTU, respectively. At the end of 24 h, the in vitro release research shows that more than 50% of naringenin has been released. Elastase and collagenase enzyme inhibitions of naringenin loaded formulations were found between 31.98 ± 0.15 and 41.74 ± 0.09%, 39.99 ± 0.19 and 47.78 ± 0.04%, respectively. Furthermore, NRF-2 and HO-1 gene expression levels did not show a significant change in the cells exposed to only naringenin loaded formulations. To conclude, developed microemulsions seem to be promising formulations that can be used for anti-aging purposes.