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Master's Dissertation
DOI
10.11606/D.42.2017.tde-07032017-151222
Document
Author
Full name
Vanessa Franco Carvalho Dartora
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Lopes, Luciana Biagini (President)
Garcia, Maria Teresa Junqueira
Santelli, Glaucia Maria Machado
Title in Portuguese
Desenvolvimento de nanocarreadores multifuncionais para co-localização cutânea de agentes quimioterápicos.
Keywords in Portuguese
Ceramida
Citotoxicidade
Nanocarreadores
Paclitaxel
Tumores cutâneos
Abstract in Portuguese
Visando o tratamento tópico de tumores cutâneos, desenvolvemos micro e nanoemulsões para a co-localização cutânea de paclitaxel e ceramida C6. A nanoemulsão mostrou-se mais eficaz em promover penetração de ambos os compostos nas camadas viáveis da pele, com aumentos de 11,5 (paclitaxel) e 3,5 (ceramida) vezes comparado a uma solução controle, e não reduziu significativamente a viabilidade de equivalentes epidérmicos, sugerindo sua segurança para aplicação tópica. A incorporação na nanoemulsão diminuiu as concentrações de paclitaxel e ceramida necessárias para reduzir a viabilidade de células de melanoma a 50% em 6 a 15 vezes, respectivamente, sendo que a co-encapsulação desses compostos promoveu uma nova redução (4 vezes) nessas concentrações, demonstrando aumento da eficácia decorrente da associação dos compostos. A administração tópica do nanocarreador contendo paclitaxel e ceramida co-encapsulados promoveu desorganização e morte celular em equivalentes cutâneos com melanoma, demonstrando o potencial desta formulação para o tratamento tópico de tumores cutâneos.
Title in English
Development of multifunctional nanocarriers for skin co-localization of chemotherapeutic agents.
Keywords in English
Ceramide
Cytotoxicity
Nanocarriers
Paclitaxel
Skin tumors
Abstract in English
Nano and microemulsions were developed in this study for cutaneous co-localization of the active agents paclitaxel and C6 ceramide for topical treatment of skin cancer. The nanoemulsion was more effective in promoting the penetration of the compounds into viable skin layers, with increases of 11.5- (paclitaxel) and 3.5- fold (ceramide) being observed. The nanoemulsion did not reduce the viability of human epidermis equivalents, suggesting its safety for topical application. Incorporation in the nanoemulsion reduced the concentration of paclitaxel and ceramide required to decrease viability of human melanoma cells to 50% by 6 to 15-fold compared with their solutions; co-encapsulation of the compounds promoted a further reduction of 4-fold. Topical administration of the nanocarrier with co-encapsulated paclitaxel and ceramide to skin equivalents with melanoma promoted disorganization and intense cytotoxicity. These results demonstrate the potential of nanoemulsions for association of paclitaxel and ceramide C6 to improve their cytotoxic effect and skin localization.
 
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Release Date
2019-03-07
Publishing Date
2017-03-07
 
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