Therapeutic deep eutectic systems as promising new tools in the anticancer battle

• Autor(a) principal: Pereira, Joana Félix
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/132853
• topic: Colorectal cancer; Deep eutectic systems; THEDES; NSAID; Natural compounds; Terpenes; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Cancer remains a major health problem worldwide, with colorectal cancer (CRC) being the third most incident and the second most lethal. Inflammation has been highly associated with cancer development and maintenance, therefore, the reduction of the inflammatory microenvironment represents a promising therapeutic strategy. Deep eutectic systems (DES) are based on the combination of different components which together, at a certain molar ratio, present a deep decrease in their melting point compared with the individual compounds. When an active pharmaceutical ingredient is part of a DES it is designated by therapeutic deep eutectic system (THEDES). New THEDES combining terpenes with anticancer properties, such as safranal, menthol and linalool, with NSAIDs, like ibuprofen, ketoprofen and flurbiprofen were produced. To evaluate THEDES therapeutic potential activity, their physico-chemical properties, bioavailability and bioactivity, were explored using an integrative approach to determine their anti-CRC activity. Our results show that Safranal:Ibuprofen (3:1), Safranal:Ibuprofen (4:1) and Menthol:Ibuprofen (3:1) present promising therapeutic activity towards CRC cells due to a selective cytotoxic action towards cancer cells. Menthol:Ibuprofen (3:1) anti proliferative action seems to be related with cell membrane disruption, reduction of the inflammation through the reduction of ROS production, and induction of apoptosis via caspase-3. On the other hand, Safranal:Ibuprofen (3:1) and Safranal:Ibuprofen (4:1) seem to prevent tumour cells expansion only through the induction of apoptosis via caspase-3. These systems also present an increasement in Ibuprofen permeability, with Menthol:Ibuprofen (3:1) increasing also Ibuprofen solubility and the overall bioavailability.