PEP-1 fused to glutathione peroxidase from Trichoderma reesei: a safe and effective antioxidant active ingredient for cutaneous applications

Author(s):Show less -

Adriani, Patricia P. ; Lopes, Luciana B. ; de Oliveira, Gabriel S. ; Nunes, Jessica R. ; Salata, Giovanna C. ; Fernandes, Myrian T. P. ; Reigado, Gustavo Roncoli ; Camarena, Denisse Esther Mallaupoma ; Maria-Engler, Silvya S. ; Dias, Marcio V. B. ; Nunes, Viviane A. ; Chambergo, Felipe S.

• Document type: Journal article
• Source: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 110, p. 11-pg., 2025-08-01.

Abstract

Skin aging is associated with an increase in the generation of reactive oxygen species (ROS), leading to progressive cellular damage. Simultaneously, the skin's antioxidant mechanisms become less effective, compromising its defense capacity. Although the use of antioxidant enzymes in cosmetic and dermatological products is promising, the topical application of these molecules is hindered by their physicochemical characteristics. An effective alternative is using cell-penetrating peptides (CPPs), which facilitate the transduction of macromolecules, including enzymes, through the skin barrier. Here, an antioxidant system composed of the glutathione peroxidase enzyme from the fungus Trichoderma reesei (TrGPx) fused to the CPP Pep-1 (PEP1-TrGPx) was developed as an alternative active antioxidant ingredient for skin treatment. The efficacy and safety of this system were evaluated as a potential cosmetic and dermatological application. The results showed that PEP1TrGPx was effectively delivered and protected human keratinocyte (HaCaT) epidermal cells against oxidative stress induced by H2O2 at low concentrations without showing a significant cytotoxic effect. Furthermore, the system demonstrated no potential for skin or ocular irritation. These findings suggest that PEP1-TrGPx is a promising, stable, safe, and effective active ingredient with great potential for therapeutic and cosmetic applications. It offers an effective strategy for skin care and mitigating oxidative stress-related damage associated with aging. (AU)

• FAPESP's process: 20/00030-0 - Enzyme system development with permeation technology for antioxidant protection in skin cells
• Grantee: Patricia Pereira Adriani
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• FAPESP's process: 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center
• Grantee: Shaker Chuck Farah
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/25705-8 - Characterization and study of Enzymes to biomass degradation.
• Grantee: Felipe Santiago Chambergo Alcalde
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/04926-6 - Melanoma and chemoresistance: in vitro and in silico models to exploit therapeutic targets
• Grantee: Silvya Stuchi Maria-Engler
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 24/03868-6 - Chemoprevention strategies for breast cancer: study of nanocarriers containing fenretinide for use in topical-transdermal therapy
• Grantee: Jessica Ribeiro Nunes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/09105-6 - Development of an enzymatic system with permeation technology for skin cell antioxidant protection
• Grantee: Patricia Pereira Adriani
• Support Opportunities: Scholarships in Brazil - Innovative Research in Small Business - PIPE
• FAPESP's process: 17/23627-0 - Determination of the structural bases of Biosynthetic formation of heterocyclic rings in ionophores polyethers
• Grantee: Gabriel Stephani de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 22/12234-5 - Resistance to antimicrobials in Mycobacterium tuberculosis: structural, biophysical and biochemical analysis of missense mutations
• Grantee: Marcio Vinicius Bertacine Dias
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/26048-6 - Development and application of multifunctional nanocarriers for intraductal delivery of chemotherapy aiming at Breast Cancer treatment
• Grantee: Giovanna Cassone Salata
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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