Modulation of the mTOR Pathway by Curcumin in the Heart of Septic Mice.

mTOR is a signaling pathway involved in cell survival, cell stress response, and protein synthesis that may be a key point in sepsis-induced cardiac dysfunction. Curcumin has been reported in vitro as an mTOR inhibitor compound; however, there are no studies demonstrating this effect in experimental sepsis. Thus, this study aimed to evaluate the action of curcumin on the mTOR pathway in the heart of septic mice. Free curcumin (FC) and nanocurcumin (NC) were used, and samples were obtained at 24 and 120 h after sepsis. Histopathological and ultrastructural analysis showed that treatments with FC and NC reduced cardiac lesions caused by sepsis. Our main results demonstrated that curcumin reduced mTORC1 and Raptor mRNA at 24 and 120 h compared with the septic group; in contrast, mTORC2 mRNA increased at 24 h. Additionally, the total mTOR mRNA expression was reduced at 24 h compared with the septic group. Our results indicate that treatment with curcumin and nanocurcumin promoted a cardioprotective response that could be related to the modulation of the mTOR pathway.

Cineole-containing nanoemulsion: Development, stability, and antibacterial activity.

1,8-cineole is a monoterpene commonly used by the food, cosmetic, and pharmaceutical industries owing to its flavor and fragrances properties. In addition, this bioactive monoterpene has demonstrated bactericidal and fungicidal activities. However, such activities are limited due to its low aqueous solubility and stability. This study aimed to develop nanoemulsion containing cineole and assess its stability and antibacterial activity in this context. The spontaneous emulsification method was used to prepare nanoemulsion (NE) formulations (F1, F2, F3, F4, and F5). Following the development of NE formulations, we chose the F1 formulation that presented an average droplet size (in diameter) of about 100 nm with narrow size distribution (PdI <0.2) and negative zeta potential (∼ - 35 mV). According to the analytical centrifugation method with photometric detection, F1 and F5 formulations were considered the most stable NE with lower droplet migration velocities. In addition, F1 formulation showed high incorporation efficiency (> 80 %) and TEM analyses demonstrated nanosized oil droplets with irregular spherical shapes and without any aggregation tendency. Antibacterial activity assessment showed that F1 NE was able to enhance the cineole action against Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pyogenes. Therefore, using a simple and reproducible method of low energy emulsification we designed a stable nanoemulsion containing 1,8-cineole with improved antibacterial activity against Gram-positive strains.

Cholesterol-rich nanoemulsion (LDE) as a novel drug delivery system to diagnose, delineate, and treat human glioblastoma.

We have prepared and characterized a cholesterol-rich nanoemulsion called LDE, a mimic of classic lipoprotein macromolecules, that can be applied as a new drug delivery system for aluminum phthalocyanine chloride (PcAlCl). The LDE containing PcAlCl system prepared herein had mean size and zeta potential of 127 nm and -29 mV, respectively, and encapsulation rate efficiency was 81%, and stability of 17 months. Compared to classical liposomes, LDE was more efficient, especially in brain diseases like glioblastoma (GBM), as revealed by tests on the U-87 MG cell line. The LDEPc formulation did not display dark cytotoxicity, as expected. The best light dose for LDEPc was 1.0 J·cm-2: its activity was 55% higher than PcAlCl in a compatible organic medium. In the U-87 MG cells, apoptosis was the preferential pathway activated by PDT. These results strongly support the use of LDE as a new theranostic system.