Reconstructed human skin model to simulate seborrheic dermatitis: evaluation of the influence of preservatives on the inflammatory process induced by bacteria and fungi of the skin microbiota

• Grant number: 22/03733-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2022
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Lorena Rigo Gaspar Cordeiro
• Grantee: Bruno Vincenzo Fiod Riccio
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Dermatitis are chronic inflammatory skin diseases that affect the skin. Seborrheic Dermatitis affects areas rich in sebaceous glands, causing erythema and desquamation and is related to yeasts of the Malassezia genus. Under physiological conditions, these yeasts are not pathogenic, however, when under pathological conditions, they express virulence factors such as proteases, lipases and form biofilms, as well as produce pro-inflammatory cytokines (IL-1±, 6 and 8, TNF-±, ²-defensin 2, among others). During infections there may be skin peeling (dandruff formation). The increase in the production of sebaceous content favors the growth of Malassezia over other microorganisms, causing them to stop living in symbiosis and enter into dysbiosis. Staphylococcus epidermidis can colonize the lesions caused by Malassezia. Cutibacterium acnes, on the other hand, can regulate the affection and growth of these microorganisms. Therefore, reconstructed human skin models can be used to study Seborrheic Dermatitis and the consequences of interactions between these microorganisms. Such models are physiologically relevant and may express pro-inflammatory factors. Furthermore, this model can be used to assess whether synthetic or natural preservatives can protect or unbalance the microbiota. Thus, the project aims to develop models of reconstructed human skin infected with microorganisms to evaluate the effect of preservatives, inflammatory response and virulence mechanisms. For this, the antimicrobial activities of these substances will be evaluated in 96-well plates. Next, the reconstructed human skin model will be developed to evaluate the incubation time and the microbial load of each microorganism (alone and in association) necessary for the infection of the proposed models for symbiosis and dysbiosis. Then, the expression of virulence factors and pro-inflammatory mediators will be evaluated, in addition to the histological evaluation. Finally, the preservatives, natural and synthetic, will be evaluated by being loaded in nanoemulsions and administered on the developed skin model. (AU)