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

Author(s)

Silva, Mariana de Sousa ; Passos, Julia S. ; Dare, Regina G. ; Nunes, Jessica R. ; Adriani, Patricia P. ; Lopes, Luciana B.

• Document type: Journal article
• Source: AAPS PHARMSCITECH; v. 26, n. 3, p. 14-pg., 2025-02-26.

Abstract

Quercetin and alpha-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 mu g/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; alpha-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 alpha-lipoic acid and the antioxidant effects in the tissue, offering a potential topical treatment for oxidative stress-related skin conditions. (AU)

• FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 19/21910-1 - Multi-User Equipment approved in grant 208/13877-1: equipment for high performance liquid chromatography (HPLC)
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 21/06755-0 - Evaluation of nanoemulsions for local-transdermal administration of fenretinide for breast cancer chemoprevention
• Grantee: Jessica Ribeiro Nunes
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 20/01208-8 - Bioadhesive nanostructured systems for intraductal administration and localized treatment of Breast Cancer
• Grantee: Julia Sapienza Passos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 22/16767-8 - Low energy methods for the obtainment of nanocarriers for topical delivery of antioxidant peptides and proteins
• Grantee: Mariana de Sousa Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/12876-7 - Study of pectin-chitosan systems enriched with nanostructured lipid carriers for the delivery of nisin, simvastatin and adenosine aiming the treatment of skin ulcers
• Grantee: Regina Gomes Daré
• Support Opportunities: Scholarships in Brazil - Post-Doctoral