A carregar...
Publicação
Pamam and ppi dendrimers as delivery systems of rose bengal to treat basal cell carcinoma: a photodynamic therapy preliminary approach
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 1.24 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
O carcinoma basocelular (BCC) é o cancro de pele mais diagnosticado em todo o mundo. Apesar de crescer lentamente e raramente metastizar, o BCC pode provocar desfiguração grave na região do tumor. Como a principal zona em que aparecem os tumores é na região da cabeça e pescoço, é muito comum que os doentes permaneçam com lesões inestéticas.
A cirurgia é a primeira linha de tratamento do BCC. Contudo, esta estratégia não é aplicável a todos os casos clínicos. A terapia fotodinâmica (PDT) surge como uma opção de tratamento promissora para os tumores de baixo risco nos casos em que a cirurgia é impraticável. A PDT apresenta excelentes resultados estéticos. As reações adversas são poucas e geralmente bem toleradas. Trata-se de um procedimento minimamente invasivo. No entanto, a PDT apresenta algumas desvantagens, principalmente relacionadas com os fotossensibilizadores (PSs) usados, tais como elevada tendência de agregação, possível toxicidade, baixa internalização celular e fraca seletividade. De forma a contornar estes problemas, surgem os dendrímeros. Os dendrímeros são sistemas de transporte promissores que podem ser úteis para melhorar as características prejudiciais dos PSs.
Esta dissertação de mestrado propõe-se a desenvolver complexos de rosa bengala (RB), um PS, com vários dendrímeros: poliamidoamina (PAMAM) G3, PAMAM G4, polipropilenimina (PPI) G3 e PPI G4. A eficiência dos quatro tipos de dendrímeros em formar complexos com a RB foi estudada recorrendo a estudos espetrofluorimétricos e à análise do potencial zeta. Para investigar se a atividade fotodinâmica da RB se mantinha após a complexação, foi realizado o ensaio de produção do singleto de oxigénio (1O2) e estudos de citotoxicidade.
Relativamente aos resultados, foi obtida uma razão molar satisfatória para todos os complexos, independentemente do tipo e da geração dos dendrímeros. O ensaio de produção de 1O2 demonstrou que mesmo ligada aos dendrímeros, a RB manteve a sua atividade fotodinâmica. Além disso, os complexos com dendrímeros G3 produziram mais 1O2 que a RB. Da mesma forma, o ensaio de MTT revelou que o comportamento da RB não foi influenciado pelos dendrímeros, pois os complexos mostraram ter uma citotoxicidade semelhante à da RB. Assim, os dendrímeros revelam ter potencial como sistemas de transportes de PSs com aplicação na PDT.
Basal cell carcinoma (BCC) is the most diagnosed skin cancer worldwide. Despite growing slowly and rarely metastasize, BCC can lead to gross disfigurement of the tumor region. As the main site for tumors is the head and neck, it is very common that patients remain with unpleasant cosmetic outcomes. Currently, surgery is the standard treatment of BCC. However, surgery is not applicable to all clinical situations. Photodynamic therapy (PDT) arises as a promising management option for low-risk BCC in the cases in which surgery is not feasible. PDT presents excellent cosmetic outcomes. Side-effects are few and generally well-tolerated. PDT is a minimally invasive procedure. However, PDT possesses some drawbacks, mainly related to the photosensitizers (PSs) used, such as high tendency to aggregate, possible toxicity, low cellular uptake and poor selectivity. In order to overcome those issues, dendrimers emerge as a possible solution. Dendrimers are promising delivery systems that could be useful to improve PSs’ detrimental characteristics. In this master thesis, we have developed complexes of rose bengal (RB), a PS, and several dendrimers: polyamidoamine (PAMAM) G3, PAMAM G4, polypropylenimine (PPI) G3 and PPI G4. The efficiency of the four types of dendrimers to form complexes with RB was studied resorting to spectrofluorimetric studies and zeta potential measurements. To investigate whether the photodynamic behavior of RB was maintained after the complexation with dendrimers, singlet oxygen (1O2) production assay and cytotoxicity studies were performed. Concerning the obtained results, a satisfactory molar ratio for all complexes was achieved, regardless of the type and generation of dendrimers. 1O2 production assay demonstrated that even when grafted on dendrimers, RB was able to keep its photodynamic properties. Moreover, G3 complexes produced more 1O2 than free RB. Likewise, MTT assay revealed that RB behavior was not influenced by dendrimers as complexes showed similar cytotoxicity as free RB. Therefore, dendrimers revealed to have potential as delivery systems of PSs with application in PDT.
Basal cell carcinoma (BCC) is the most diagnosed skin cancer worldwide. Despite growing slowly and rarely metastasize, BCC can lead to gross disfigurement of the tumor region. As the main site for tumors is the head and neck, it is very common that patients remain with unpleasant cosmetic outcomes. Currently, surgery is the standard treatment of BCC. However, surgery is not applicable to all clinical situations. Photodynamic therapy (PDT) arises as a promising management option for low-risk BCC in the cases in which surgery is not feasible. PDT presents excellent cosmetic outcomes. Side-effects are few and generally well-tolerated. PDT is a minimally invasive procedure. However, PDT possesses some drawbacks, mainly related to the photosensitizers (PSs) used, such as high tendency to aggregate, possible toxicity, low cellular uptake and poor selectivity. In order to overcome those issues, dendrimers emerge as a possible solution. Dendrimers are promising delivery systems that could be useful to improve PSs’ detrimental characteristics. In this master thesis, we have developed complexes of rose bengal (RB), a PS, and several dendrimers: polyamidoamine (PAMAM) G3, PAMAM G4, polypropylenimine (PPI) G3 and PPI G4. The efficiency of the four types of dendrimers to form complexes with RB was studied resorting to spectrofluorimetric studies and zeta potential measurements. To investigate whether the photodynamic behavior of RB was maintained after the complexation with dendrimers, singlet oxygen (1O2) production assay and cytotoxicity studies were performed. Concerning the obtained results, a satisfactory molar ratio for all complexes was achieved, regardless of the type and generation of dendrimers. 1O2 production assay demonstrated that even when grafted on dendrimers, RB was able to keep its photodynamic properties. Moreover, G3 complexes produced more 1O2 than free RB. Likewise, MTT assay revealed that RB behavior was not influenced by dendrimers as complexes showed similar cytotoxicity as free RB. Therefore, dendrimers revealed to have potential as delivery systems of PSs with application in PDT.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Basal cell carcinoma Photodynamic therapy Dendrimers Rose bengal Mestrado integrado - 2020