Impacto na migração de queratinócitos por modulação das enzimas LOX : aplicabilidade em formulações tópicas cutâneas

Abstract

A skin wound is defined by any alteration in the integrity of the skin layers. It is estimated that 2 million Europeans suffer from skin lesions, which is an important factor influencing the patient's quality of life. When the skin is disrupted, the integumentary system has the capacity to self-regenerate, a process called healing of skin lesions. It constitutes a vital and fundamental process whose main objective is to restore the integrity and normal function of the skin, where numerous cellular components are involved, such as the LOX enzymes. These catalyze cross-linking reactions of collagen and elastin in connective tissue, thus allowing cross-linking between these two compounds in the extracellular matrix of the skin, facilitating the process of cell migration in the wound healing process. In order to optimize treatments to maximize the healing of cutaneous wounds, the present dissertation had as main objective to study the impact of selected compounds, with inhibitory activity of LOX enzymes, in the collective migration of keratinocytes, and later development of nanoformulations for cutaneous application, having with a view to optimizing the healing process of cutaneous wounds, contributing to the improvement of problems related to these and possibly increasing the patient's quality of life. Using an in vitro assay, the effect of LOX BAPN, EPCU-5 and PN1 inhibitor compounds on collective migration of HaCaT cells was evaluated. Contrary to what would be expected considering the effect of this type of compounds on other cell lines, it was observed that two of the compounds significantly increased collective cell migration, while another compound did not have any impact on cell migration. Subsequently, nanoformulations composed of solid lipid nanoparticles containing BAPN were produced and developed and their stability over time was evaluated, as well as their impact when applied to the skin. In general, the developed nanoformulations showed stable pH, hydrodynamic diameter and polydispersion index values over the 30 days of the study. The results of the in vivo study indicate a good cutaneous compatibility of the nanoformulations, but no differences were observed regarding the control in its effectiveness, so future studies with a larger panel of volunteers will be necessary. Keywords: LOX enzymes, wound healing, risk assay, collective cell migration, nanotechnology, skin application

Date of Award	2023
Original language	Portuguese
Supervisor	Nuno Saraiva (Supervisor)