Transportadores lipídicos nanoestruturados inspirados na composição do estrato córneo : uma abordagem inovadora para promover o reforço da barreira cutânea
Miniatura indisponível
Ficheiros
Data
2023
Título da revista
ISSN da revista
Título do Volume
Editora
Resumo
As alterações na composição lipídica do estrato córneo (EC) estão relacionadas com diversas patologias cutâneas que acometem a integridade da barreira, como a psoríase, a dermatite atópica, a xerose e a ictiose. No entanto, os sistemas de veiculação convencionais à base de corticoides tópicos apresentam algumas limitações, daí a necessidade de investir no desenvolvimento de sistemas inovadores que permitam aumentar a relação risco-benefício do tratamento. Assim, o trabalho experimental realizado teve como objetivo o desenvolvimento de transportadores lipídicos nanoestruturados (NLC) como sistemas de veiculação do 21-acetato de hidrocotisona (AH), constituídos por ácidos gordos semelhantes aos presentes naturalmente no EC, de forma a promover o reforço da barreira cutânea.
Inicialmente, foram realizados estudos de pré-formulação para seleção do lípido líquido e do(s) lípido(s) sólido(s), concentração do tensioativo, bem como do tempo de sonicação. Posteriormente, foram avaliadas as propriedades físico-químicas das formulações de NLC, bem como foram realizados estudos de estabilidade acelerada e a longo prazo (90 dias). Para além disso, recorreu-se a testes in vivo para avaliar a segurança e eficácia dos NLCs. Procedeu-se ainda à incorporação do AH nas formulações de NLC mais promissoras, tendo sido realizados estudos de caracterização físico-química, bem como estudos de estabilidade acelerada.
Os resultados obtidos indicaram que os lípidos sólidos incorporados têm influência nas propriedades físico-químicas e na estabilidade dos NLCs, principalmente quando em associação (ácido esteárico:Precirol® ATO5 1:1). Contudo, as nanoformulações mais promissoras, constituídas apenas por Precirol® ATO5, apresentaram propriedades adequadas para aplicação cutânea em termos de tamanho de partícula, índice de polidispersão, pH e viscosidade, bem como boa compatibilidade cutânea e capacidade para promover a hidratação cutânea. No que diz respeito à incorporação de AH e, embora se tenha observado um aumento no tamanho da partícula, as nanoformulações apresentaram valores razoavelmente apropriados para aplicação cutânea. No entanto, os NLCs contendo AH apresentaram sinais de instabilidade (formação de um precipitado), o que poderá indicar a incorporação deficitária do fármaco e/ou problemas ao nível da solubilidade. Ainda assim, os resultados obtidos no geral representam um avanço significativo quanto à utilização deste tipo de nanossistemas para promover um reforço da barreira cutânea.
Palavras-chave: estrato córneo; transportadores lipídicos nanoestruturados; glucocorticoides tópicos; patologias cutâneas
Variations in stratum corneum (SC) lipid composition are related to several skin diseases that affect the barrier integrity, such as psoriasis, atopic dermatitis, xerosis and ichthyosis. However, conventional delivery systems based on topical corticosteroids have some limitations, hence the need to invest in developing innovative systems that increase the treatment’s risk-benefit ratio. Thus, the experimental work carried out aimed to develop nanostructured lipid carriers (NLC) as delivery systems for hydrocortisone 21-acetate (HA), consisting of fatty acids similar to those naturally present in SC, to promote the skin barrier reinforcement. Initially, pre-formulation studies were performed to select the liquid lipid and solid lipid(s), surfactant concentration, as well as sonication time. Subsequently, the physicochemical properties of the NLC formulations were evaluated, and studies on accelerated and long-term (90 days) stability were performed. In addition, in vivo tests were used to evaluate the safety and efficacy of the NLCs. AH was also incorporated into the most promising NLC formulations, and physicochemical characterization studies were performed, as well as accelerated stability studies. The data obtained indicated that the solid lipids incorporated have an influence on the physicochemical properties and stability of NLCs, especially when in association (stearic acid:Precirol® ATO5 1:1). However, the most promising nanoformulations, made of Precirol® ATO5, showed suitable properties for cutaneous application in terms of particle size, polydispersity index, pH, and viscosity, as well as good skin compatibility and capacity to promote skin hydration. Regarding AH incorporation, even though an increase in particle size was observed, the nanoformulations showed reasonably appropriate values for cutaneous application. However, the AH-containing NLCs showed signs of instability (formation of a precipitate), which may indicate deficient incorporation of the drug and/or solubility problems. Nevertheless, the results obtained represent a significant advance regarding the use of this type of nanosystems to promote the reinforcement of the skin barrier. Keywords: stratum corneum; nanostructured lipid carriers; topical corticosteroids; cutaneous pathologies
Variations in stratum corneum (SC) lipid composition are related to several skin diseases that affect the barrier integrity, such as psoriasis, atopic dermatitis, xerosis and ichthyosis. However, conventional delivery systems based on topical corticosteroids have some limitations, hence the need to invest in developing innovative systems that increase the treatment’s risk-benefit ratio. Thus, the experimental work carried out aimed to develop nanostructured lipid carriers (NLC) as delivery systems for hydrocortisone 21-acetate (HA), consisting of fatty acids similar to those naturally present in SC, to promote the skin barrier reinforcement. Initially, pre-formulation studies were performed to select the liquid lipid and solid lipid(s), surfactant concentration, as well as sonication time. Subsequently, the physicochemical properties of the NLC formulations were evaluated, and studies on accelerated and long-term (90 days) stability were performed. In addition, in vivo tests were used to evaluate the safety and efficacy of the NLCs. AH was also incorporated into the most promising NLC formulations, and physicochemical characterization studies were performed, as well as accelerated stability studies. The data obtained indicated that the solid lipids incorporated have an influence on the physicochemical properties and stability of NLCs, especially when in association (stearic acid:Precirol® ATO5 1:1). However, the most promising nanoformulations, made of Precirol® ATO5, showed suitable properties for cutaneous application in terms of particle size, polydispersity index, pH, and viscosity, as well as good skin compatibility and capacity to promote skin hydration. Regarding AH incorporation, even though an increase in particle size was observed, the nanoformulations showed reasonably appropriate values for cutaneous application. However, the AH-containing NLCs showed signs of instability (formation of a precipitate), which may indicate deficient incorporation of the drug and/or solubility problems. Nevertheless, the results obtained represent a significant advance regarding the use of this type of nanosystems to promote the reinforcement of the skin barrier. Keywords: stratum corneum; nanostructured lipid carriers; topical corticosteroids; cutaneous pathologies
Descrição
Orientação: Catarina Pereira Leite ; coorientação: Catarina Rosado
Palavras-chave
MESTRADO INTEGRADO EM CIÊNCIAS FARMACÊUTICAS, CIÊNCIAS FARMACÊUTICAS, PHARMACEUTICAL SCIENCES, SISTEMAS DE LIBERTAÇÃO DE MEDICAMENTOS, DRUG DELIVERY SYSTEMS, LÍPIDOS, LIPIDS, GLUCOCORTICOIDES, GLUCOCORTICOIDS, DOENÇAS DA PELE, SKIN DISEASES