Nanopartículas lipídicas sólidas inspiradas na composição do estrato córneo : uma abordagem inovadora para promover o reforço da barreira cutânea
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2023
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A maioria das funções epidérmicas de barreira são consideradas protetoras e estão diretamente ligadas ao estrato córneo (EC), que possui uma organização e composição única, essencial para a manutenção desta propriedade. Contudo, a desregulação desta função devido a distúrbios na composição e/ou organização lipídica do EC podem potenciar o desenvolvimento de disfunções ou patologias inflamatórias na pele.
O principal objetivo desta dissertação foi o desenvolvimento de nanopartículas lipídicas sólidas (SLN) com uma constituição lipídica semelhante ao EC para o tratamento de patologias e disfunções associadas ao comprometimento da barreira epidérmica. Para esse fim, três formulações constituídas por lípidos sólidos diferentes foram produzidas e caracterizadas segundo tamanho, índice de polidispersão (PDI), pH e viscosidade. As nanoformulações foram também submetidas a estudos de estabilidade acelerada e estabilidade a longo prazo. Adicionalmente, efetuaram-se ensaios in vivo para avaliação da compatibilidade cutânea, considerando uma aplicação aberta e sob oclusão das formulações. Por último, a eficácia das SLN desenvolvidas foi estudada em voluntários humanos, em que se avaliou o seu caráter potenciador da hidratação cutânea.
Os resultados obtidos revelaram-se promissores, com valores considerados adequados para aplicação tópica no que se refere ao tamanho, PDI, pH e viscosidade das formulações. Relativamente à sua estabilidade, as mesmas demonstraram estabilidade quando sujeitas a ambientes de stress físico e térmico. Por outro lado, em condições de armazenamento controladas (25 ± 2 °C) durante um período de 90 dias, a formulação SLN_2, constituída por Precirol® ATO 5, foi a que se demonstrou mais promissora, considerando os 4 parâmetros analisados. A aplicação aberta ou sob oclusão das formulações demonstrou ser compatível com a pele, já que não se verificaram alterações nos diversos parâmetros analisados. Adicionalmente, após uma aplicação de 4 h da formulação SLN_2, pode comprovar-se uma melhoria dos níveis de hidratação da pele. Desta forma, estes resultados revelam o caráter promissor que as nanoformulações desenvolvidas possuem para aplicações tópicas em indivíduos portadores de patologias ou disfunções cutâneas associadas ao comprometimento da barreira epidérmica.
Palavras-chave: Nanopartículas lipídicas sólidas; aplicação tópica; compatibilidade cutânea; bioengenharia cutânea
Most epidermal barrier functions are considered protective and are directly linked to the stratum corneum (SC), which has a unique organization and composition, essential for maintaining this property. However, the deregulation of this function due to disturbances in the lipid composition and/or organization of the SC may trigger the development of inflammatory pathologies or dysfunctions in the skin. In this context, the main objective of this dissertation was the development of solid lipid nanoparticles (SLN) with a lipid constitution similar to SC for the treatment of pathologies and dysfunctions associated with the impairment of the epidermal barrier. For this purpose, three formulations consisting of different solid lipids were produced and characterized according to size, polydispersity index (PDI), pH and viscosity. The nanoformulations were also submitted to accelerated stability and long-term stability studies. Additionally, in vivo tests were carried out to assess their skin compatibility in human volunteers, considering an open or under occlusion application of the formulations. Lastly, the analysis of the efficacy of the developed SLN was carried out also in human volunteers, in which their ability to enhance skin hydration was evaluated. The results obtained were promising, with values considered adequate for topical application in terms of size, PDI, pH, and viscosity of the formulations. Regarding their stability, they were stable when subjected to environments of physical and thermal stress. On the other hand, in controlled storage conditions (25 ± 2 °C) for a period of 90 days, the SLN_2 formulation, consisting of Precirol® ATO 5, was the most promising, considering the 4 parameters analyzed. The open or under occlusion application of the formulations proved to be compatible with the skin, since there were no changes in the various parameters analyzed. Additionally, after a 4 h application period of the SLN_2 formulation, an improvement in skin hydration levels were observed. Thus, these results reveal the potential of the developed nanoformulations for topical applications in individuals with cutaneous pathologies or dysfunctions associated with the impairment of the epidermal barrier. Keywords: Solid lipid nanoparticles; topical application; skin compatibility; skin bioengineering.
Most epidermal barrier functions are considered protective and are directly linked to the stratum corneum (SC), which has a unique organization and composition, essential for maintaining this property. However, the deregulation of this function due to disturbances in the lipid composition and/or organization of the SC may trigger the development of inflammatory pathologies or dysfunctions in the skin. In this context, the main objective of this dissertation was the development of solid lipid nanoparticles (SLN) with a lipid constitution similar to SC for the treatment of pathologies and dysfunctions associated with the impairment of the epidermal barrier. For this purpose, three formulations consisting of different solid lipids were produced and characterized according to size, polydispersity index (PDI), pH and viscosity. The nanoformulations were also submitted to accelerated stability and long-term stability studies. Additionally, in vivo tests were carried out to assess their skin compatibility in human volunteers, considering an open or under occlusion application of the formulations. Lastly, the analysis of the efficacy of the developed SLN was carried out also in human volunteers, in which their ability to enhance skin hydration was evaluated. The results obtained were promising, with values considered adequate for topical application in terms of size, PDI, pH, and viscosity of the formulations. Regarding their stability, they were stable when subjected to environments of physical and thermal stress. On the other hand, in controlled storage conditions (25 ± 2 °C) for a period of 90 days, the SLN_2 formulation, consisting of Precirol® ATO 5, was the most promising, considering the 4 parameters analyzed. The open or under occlusion application of the formulations proved to be compatible with the skin, since there were no changes in the various parameters analyzed. Additionally, after a 4 h application period of the SLN_2 formulation, an improvement in skin hydration levels were observed. Thus, these results reveal the potential of the developed nanoformulations for topical applications in individuals with cutaneous pathologies or dysfunctions associated with the impairment of the epidermal barrier. Keywords: Solid lipid nanoparticles; topical application; skin compatibility; skin bioengineering.
Descrição
Orientação: Catarina Pereira Leite ; coorientação: Catarina Rosado
Palavras-chave
MESTRADO INTEGRADO EM CIÊNCIAS FARMACÊUTICAS, CIÊNCIAS FARMACÊUTICAS, PHARMACEUTICAL SCIENCES, NANOPARTÍCULAS LIPÍDICAS SÓLIDAS, SOLID LIPID NANOPARTICLES, ADMINISTRAÇÃO CUTÂNEA, CUTANEOUS ADMINISTRATION