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

Abstract

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.