| Texto completo | |
| Autor(es): |
Viegas, Juliana Santos Rosa
;
Araujo, Jackeline Souza
;
Leite, Marcel Nani
;
Praca, Fabiola Garcia
;
Del Ciampo, Jose Orestes
;
Espreafico, Enilza Maria
;
Frade, Macro Andrey Cipriani
;
Bentley, Maria Victoria Lopes Badra
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | DRUG DELIVERY AND TRANSLATIONAL RESEARCH; v. N/A, p. 16-pg., 2024-09-02. |
| Resumo | |
Multifunctional therapies have emerged as innovative strategies in cancer treatment. In this research article, we proposed a nanostructured lipid carrier (NLC) designed for the topical treatment of cutaneous melanoma, which simultaneously delivers 5-FU and Bcl-2 siRNA. The characterized nanoparticles exhibited a diameter of 259 +/- 9 nm and a polydispersion index of 0.2, indicating a uniform size distribution. The NLCs were primarily localized in the epidermis, effectively minimizing the systemic release of 5-FU across skin layers. The ex vivo skin model revealed the formation of a protective lipid film, decreasing the desquamation process of the stratum corneum which can be associated to an effect of increasing permeation. In vitro assays demonstrated that A375 melanoma cells exhibited a higher sensitivity to the treatment compared to non-cancerous cells, reflecting the expected difference in their metabolic rates. The uptake of NLC by A375 cells reached approximately 90% within 4 h. The efficacy of Bcl-2 knockdown was thoroughly assessed using ELISA, Western blot, and qRT-PCR analyses, revealing a significant knockdown and synergistic action of the NLC formulation containing 5-FU and Bcl-2 siRNA (at low concentration --100 pM). Notably, the silencing of Bcl-2 mRNA also impacted other members of the Bcl-2 protein family, including Mcl-1, Bcl-xl, BAX, and BAK. The observed modulation of these proteins strongly indicated the activation of the apoptosis pathway, suggesting a successful inhibition of melanoma growth and prevention of its in vitro spread. (AU) | |
| Processo FAPESP: | 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar |
| Beneficiário: | Maria Vitória Lopes Badra Bentley |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |