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.

Background: Acquired resistance and adverse effects are some of the challenges faced by thousands of Luminal A breast cancer patients under tamoxifen (TMX) treatment. Some authors associate the overexpression of HOXB7 with TMX resistance in this molecular subtype, and the knockdown of this gene could be an effective strategy to regain TMX sensitivity. Therefore, we used calcium phosphate hybrid nanoparticles (HNP) for the delivery of short interfering RNA molecule (siRNA) complementary to the HOXB7 gene and evaluated the RNA interference (RNAi) effects associated with TMX treatment in breast cancer in vivo. Methods: HNP were prepared by the self-assembly of a methoxy-poly (ethylene glycol)-block-poly (L-glutamic acid) copolymer (PEG-pGlu) and the coprecipitation of CaPO₄ to incorporate siRNA. The in vitro cell viability and migration were evaluated prior to in vivo experiments. Further, animals bearing early-stage and advanced Luminal A breast cancer were treated with HNP-siHOXB7, HNP-siHOXB7 + TMX, and TMX. Antitumoral activity and gene expression were evaluated following histopathological, hematological, and biochemical analysis. Results: The HNP were efficient in delivering the siRNA in vitro and in vivo, whilst HOXB7 silencing associated with TMX administration promoted controlled tumor growth, as well as a higher survival rate and reduction in immuno- and hepatotoxicity. Conclusions: Therefore, our findings suggest that HOXB7 can be an interesting molecular target for Luminal A breast cancer, especially associated with hormone therapy, aiming for adverse effect mitigation and higher therapeutic efficacy.

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.

The authors report the effects of bee venom and isolated melittin against triple negative breast cancer cells in comparison to MCF10A normal breast tissue. The methodology is well established, in accordance with the main objectives and is capable of...