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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2020.tde-22012020-120448
Document
Author
Full name
Daniel Augusto Gomes Miranda
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Lopes, Luciana Biagini (President)
Andréo Filho, Newton
Chacra, Nádia Araci Bou
Rodrigues, Alice Cristina
Title in Portuguese
Sistema nanoestruturado para a localização cutânea de compostos doadores de H2S visando o tratamento de psoríase.
Keywords in Portuguese
Co-localização
Doador H2S
Fase lamelar.
Pró-fármaco
Sistema nanoestruturado
Abstract in Portuguese
A psoríase é uma doença inflamatória crônica, imunomediada, que se apresenta de diversas formas e impacta a qualidade de vida dos pacientes. O tratamento é feito conforme a gravidade da doença; no caso da doença leve a moderada, o tratamento geralmente é tópico utilizando corticoide. Entretanto, esse tratamento apresenta diversos efeitos adversos, principalmente em decorrência dos efeitos sistêmicos dos corticoides. Aqui propomos a associação de corticoides a doadores de H2S na forma de um novo pró-fármaco (dexametasona-TBZ e dexametasona-ADT), a fim de potencializar o efeitos anti-inflamatórios sem a necessidade de aumentar a dose aplicada do corticoide, de modo a restringir efeitos adversos. Desenvolvemos 2 grupos de formulações variando o tensoativo e a fase oleosa. Em ambos os grupos, o tipo de fase formada foi dependente do teor de água: sistemas contendo 20 e 70% de água formaram fase lamelar e dispersão estabilizada por fase lamelar, respectivamente. As dispersões apresentaram duas populações com diâmetro variando até 1000 nm e potencial zeta negativo. Todas as formulações apresentaram comportamento reológico do tipo pseudoplástico. A força necessária para destacar as formulações A e B contendo 20% de água da pele foi 1,5-1,9 vezes superior comparado à água, indicando potencial bioadesivo das formulações. A dexa-TBZ foi incorporada a 1%, e sua estabilidade nas formulações foi demonstrada por 8 h, mesmo naquelas contendo 70% de água. As formulações A com 20% (A-20) e 70% (A-70) de água promoveram acantose. As formulações do grupo B promoveram aumento na penetração cutânea do pró-fármaco, sendo a penetração no estrato córneo e epiderme viável 1,9-2,2 vezes (B-20) e 1,7-2,6 vezes (B-70) maior quando comparados ao controle. Selecionamos B-70 para os estudos in vivo em camundongos com psoríase induzida por imiquimode. Os pró-fármacos são eficazes na redução de parâmetros inflamatórios em camundongos com psoríase experimental, mas esses efeitos são semelhantes ao tratamento convencional (dexametasona).
Title in English
Nanoestrutured systems for the cutaneous delivery of H2S donor compounds for treatment of psoriasis.
Keywords in English
Co-drug
Co-localization
Donor H2S
Lamellar phase.
Nanostructured system
Abstract in English
Psoriasis is a chronic inflamatory disease, immune-mediated, that occurs in various forms, causing major psychosocial impact and decreases in the quality of life of patients. Treatment varies according to the severity of the disease; in the case of mild- to-moderate disease, the standard treatment is topical corticosteroids. However, this treatment has several adverse effects, mainly due to the systemic effects of corticosteroids. Here we propose the association of corticosteroids to H2S donors (dexamethasone-TBZ and dexamethasone-ADT) in the form of a new codrug in order to potentiate the anti-inflammatory effects without the need to increase the applied dose of the corticosteroid, reducing the incidence of adverse effects. We developed two groups of formulations varying the surfactant and the oil phase. In both groups, the type of phase formed was dependent on the water content: systems containing 20 and 70% water formed lamellar phase and dispersion stabilized by lamellar phase, respectively. The dispersions had two populations with a diameter ranging up to 1000 nm and negative zeta potential. All formulations showed pseudoplastic rheological behavior. The dexamethasone-TBZ was incorporated at 1%, and its stability in the formulations was demonstrated for 8 h, even for those containing 70% water. Formulations A with 20% (A-20) and 70% (A-70) of water promoted acanthosis. The formulations of group B increased skin penetration of the codrug, and 1.9-2.2 times (B- 20) and 1.7-2.6 times (B-70) more drug was quantified in the stratum corneum and epidermis compared to the control. We selected B-70 for in vivo studies in mice with psoriasis induced for imiquimode. The codrugs were effective in reducing inflammatory parameters in mice with experimental psoriasis, but these effects are similar to conventional treatment (dexamethasone).
 
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Release Date
2024-03-21
Publishing Date
2020-01-28
 
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