The main function of the skin is to protect the body from the external environment. However, the skin can undergo inflammatory processes, due to genetic, hormonal, or environmental factors. When the defense system is overloaded, there is an increase in pro-inflammatory mediators and reactive oxygen species (ROS), which results in skin disorders. Among the substances used to treat these inflammatory processes, many natural substances with anti-inflammatory and antioxidant properties are being studied: nature is yet an abundant source to obtain diverse pharmacological actives. The treatment of skin diseases is usually focused on topical application, as it reduces the risk of systemic side effects and prevents drug degradation by first-pass metabolism. Thus, the properties of drug delivery vehicles can facilitate or inhibit its permeation. Due to the hydrophobic nature of the skin, a promising strategy to improve dermal drug penetration is the use of lipid-based nanoparticles, such as nanostructured lipid carriers (NLC). Therefore, in this review, we present NLC as a tool to improve dermal administration of natural substances with anti-inflammatory properties.
Breast cancer is the most common type of cancer that affects and kills women annually in the world. It impacts more than two million women and is responsible for the death of approximately 25% of them. Almost 70% of breast cancer diagnoses are positive for hormone receptor and have a good prognosis. However, resistance to drugs used in hormone therapy, such as tamoxifen, is usual and about 40% of recurrences do not respond to it. In some cases, the overexpression of the HOXB7 gene is related to this mechanism and its silencing can reverse the response to tamoxifen. Here, we used copolymer-coated calcium phosphate nanoparticles to deliver HOXB7 siRNA and restore the sensitization of MCF7 cells to tamoxifen. Nanoparticle synthesis and characterization were performed, and cell viability and gene expression were evaluated. Hybrid nanoparticle presented a Z-average diameter of 83 nm and polydispersity index (PdI) of 0.07, while showing good entrapment of siRNA molecules. We also observed a decrease in HOXB7 gene expression (~65%) promoted by the siRNA molecule delivered by the nanoparticles. The gene silencing has good correlation to the cell viability assay: a reduction in breast cancer viability was observed in 48 (31%) and 72 (38%) hours. As for the co-treatment with tamoxifen, cell viability started dropping after 15 h, which did not occur in the treatment only with Tamoxifen at the same concentration. This result indicates that the biological effect was possibly related to RNAi effect and suggests that HOXB7 may be promoting cell sensitization to tamoxifen without reducing cell viability. Overall, these results suggest that the nanostructured system was effective in promoting gene silencing and that the co-therapy can be a promising tool for the treatment of hormone receptor-positive breast cancers.
Este estudo propõe preparar sistemas nanocarreadores para solubilização e incorporação de ativos hidrofóbicos e realizar sua caracterização físico-química. Um sistema nanoparticulado composto por lipídios de origem natural e copolímeros em bloco foi designado para a incorporação de dois ativos hidrofóbicos, constituindo duas formulações nanoestruturadas diferentes. Após a determinação do ponto de fusão e perfil cromatográfico da manteiga natural empregada, as formulações foram preparadas por fusão-emulsificação, sendo aquecidas e homogeneizadas em aparelhos apropriados. Em seguida, as formulações foram caracterizadas por Espalhamento Dinâmico de Luz. As formulações 1 e 2 obtiveram um tamanho de 124,8 ± 0,31nm e 271,9 ± 0,28nm; índice de polidispersão 0,249 ± 0,09 e 0,255 ± 0,07; potencial zeta -15,3 ± 0,78mV e -11,8 ± 0,92mV, respectivamente. Imagens obtidas por Microscopia Eletrônica de Transmissão indicam um formato esférico das partículas com média de tamanho de aproximadamente 200nm. O método elaborado revelou-se eficaz para a solubilização dos ativos hidrofóbicos testados: houve formação de nanoestruturas incorporando os ativos nas condições avaliadas, com características fisico-químicas apropriadas para aplicação farmacêutica.
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