Mayara R. dos Santos

Abstract Several efforts have been extensively accomplished for the amelioration of the cancer treatments using different types of new drugs and less invasives therapies in comparison with the traditional therapeutic modalities, which are widely associated with numerous drawbacks, such as drug resistance, non-selectivity and high costs, restraining their clinical response. The application of natural compounds for the prevention and treatment of different cancer cells has attracted significant attention from the pharmaceuticals and scientific communities over the past decades. Although the use of nanotechnology in cancer therapy is still in the preliminary stages, the application of nanotherapeutics has demonstrated to decrease the various limitations related to the use of natural compounds, such as physical/chemical instability, poor aqueous solubility, and low bioavailability. Despite the nanotechnology has emerged as a promise to improve the bioavailability of the natural compounds, there are still limited clinical trials performed for their application with various challenges required for the pre-clinical and clinical trials, such as production at an industrial level, assurance of nanotherapeutics long-term stability, physiological barriers and safety and regulatory issues. This review highlights the most recent advances in the nanocarriers for natural compounds secreted from plants, bacteria, fungi, and marine organisms, as well as their role on cell signaling pathways for anticancer treatments. Additionally, the clinical status and the main challenges regarding the natural compounds loaded in nanocarriers for clinical applications were also discussed.

Abstract Lipid nanoparticles (LN) composed of biodegradable lipids and produced by green methods are candidates for the encapsulation of pesticides, potentially contributing to decreasing their release in the environment. From a safety-by-design concept, this work proposes LN for the encapsulation of insecticide active ingredients (AI). However, given the complexity of nanoparticles, ecotoxicological studies are often controversial, and a detailed investigation of their effects on the environment is required. Accordingly, this work aimed to produce and characterize LN containing the insecticide lambda-cyhalothrin (LC) and evaluate their safety to crops (Solanum lycopersicum and Zea mays), soil invertebrates (Folsomia candida and Eisenia fetida), and soil microbial parameters. The average particle size for LN-loaded with LC (LN-LC) was 165.4 +/- 2.34 nm, with narrow size distribution and negative charge (-38.7 +/- 0.954 mV). LN were able to encapsulate LC with an entrapment efficacy of 98.44 +/- 0.04%, maintaining the stability for at least 4 months. The LN-LC showed no risk to the growth of crops and reproduction of the invertebrates. The effect on microbial parameters showed that the activity of certain soil microbial parameters can be inhibited or stimulated by the presence of LN at highest concentrations, probably by changing the pH of soil or by the intrinsic properties of LN.

Abstract <jats:title>Abstract</jats:title><jats:p>Leishmaniasis is a neglected disease caused by protozoan parasites of the <jats:italic>Leishmania</jats:italic> genus. Benzylamines are a class of compounds selectively designed to inhibit the squalene synthase (SQS) that catalyzes the first committed reaction on the sterol biosynthesis pathway. Herein, we studied seven new benzylamines (SBC 37–43) against <jats:italic>Leishmania amazonensis</jats:italic>. After the first screening of cell viability, two inhibitors (SBC 39 and SBC 40) were selected. Against intracellular amastigotes, SBC 39 and SBC 40 presented selectivity indexes of 117.7 and 180, respectively, indicating high selectivity. Analysis of the sterol composition revealed a depletion of endogenous 24-alkylated sterols such as episterol and 5-dehydroepisterol, with a concomitant accumulation of fecosterol, implying a disturbance in cellular lipid content. This result suggests a blockade of de novo sterol synthesis at the level of SQS and C-5 desaturase. Furthermore, physiological analysis and electron microscopy revealed three main alterations: (1) in the mitochondrion; (2) the presence of lipid bodies and autophagosomes; and (3) the appearance of projections in the plasma membrane. In conclusion, our results support the notion that benzylamines have a potent effect against <jats:italic>Leishmania amazonensis</jats:italic> and should be an exciting novel pharmaceutical lead for developing new chemotherapeutic alternatives to treat leishmaniasis.</jats:p>