Microemulsions Improve the Cutaneous Co-Localization of Lipoic Acid and Quercetin and Antioxidant Effects in Cutaneous Cells and Tissue

Abstract

Quercetin and α-lipoic acid are antioxidants with potential applications in the treatment of various skin conditions, such as wounds and chemoprevention of skin cancer. To enable their effective topical co-delivery and co-localization in the tissue, we developed microemulsions (ME). The selected ME (ME-50) formed a stable system with a mean droplet size of 134.4 ± 17.9 nm, increasing to 224.9 ± 19.9 nm upon antioxidants co-incorporation. The ME preserved the antioxidant capacities of the molecules, with DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assay showing an IC₅₀ of 6.2 ± 0.1 µg/mL, similar to the solution. Skin penetration studies revealed a 2.4-fold increase in quercetin (Q) accumulation in the stratum corneum and a 3.5-fold increase in the delivery to viable epidermis and dermis (ED) after a 12 h-treatment with the ME compared to control solutions; α-lipoic acid (LA) penetration improved up to 1.9-fold in ED upon ME incorporation. Treatment with Q + LA co-loaded ME enhanced the antioxidant activity in the stratum corneum and ED by 1.3-fold and 2.0-fold, respectively, compared to solutions. Treatment with the ME for 24 h also reduced oxidative species levels by 55% in H₂O₂-exposed keratinocytes compared to the control (untreated) cells. Taken together, these results suggest that ME-50 is a promising delivery system for enhancing the cutaneous co-delivery of quercetin and α-lipoic acid and the antioxidant effects in the tissue, offering a potential topical treatment for oxidative stress-related skin conditions.

Graphical Abstract