STUDIES OF FORMULATION AND BIOLOGICAL EFFECT OF PHOTOLYASE IN IN VITRO SKIN MODELS AIMING AT PHOTOPROTECTION AND PREVENTION OF SKIN AGING

• Grant number: 23/17651-6
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2024
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Carlota de Oliveira Rangel Yagui
• Grantee: Carlota de Oliveira Rangel Yagui
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Silvya Stuchi Maria-Engler ; Valker Araujo Feitosa
• Associated scholarship(s): 25/04170-5 - CUTANEOUS PENETRATION OF FREE, PEGYLATED AND NANOENCAPSULATED CATALASE, BP.IC; 25/00654-8 - INFLUENCE OF POLYMERSOMES COMPOSITION ON THE CAPACITY TO PROMOTE PROTEIN PENETRATION INTO THE SKIN, BP.IC

Abstract

The increasing exposition to ultraviolet (UV) radiation has been causing health and aesthetic problems, both acutely (hyperpigmentation, sunburn, inflammatory reactions, photoallergy and photosensitivity) and chronically (skin cancer, immunosuppression and photoaging). Chronic effects are in part related to UV-induced damage to DNA and enzymes such as photolyase, capable of increasing the endogenous capacity of DNA repair, are an interesting alternative to prevent this damage. This enzyme can increase protection against UV radiation, reducing photoaging and photocarcinogenesis. Nonetheless, photolyase safety to human skin and topical characteristics still need elucidation, especially since up to now only plankton extracts are used in commercial products as a source of photolyase. On the other hand, owing to the protein structure photolyase presents challenges for topical use and nanostructures such as polymersomes can be an interesting alternative to the classic liposomes for the enzyme formulation. As a sequence of our previous studies with photolyase in queratinocytes cell culture (monolayer) and poloxamer 401 polymersomes, in this project we will evaluate the effect T. thermophilus photolyase recombinantly expressed in E. coli in reconstituted human epidermis model (RHE). More specifically, we will investigate the enzyme cytotoxicity, the DNA repair activity and the polymersomes cytotoxicity and potential to promote skin penetration. Aiming at improving the nanostructured systems, we will also investigate mixed formulations of poloxamer 401 and semi-crystalline copolymers that might result in more stable formulations for future cosmetic/therapeutic applications. (AU)