piperidines and geraniol

The most important arboviruses are those that cause dengue, yellow fever, chikungunya, and Zika, for which the main vector is the

Topics: Acyclic Monoterpenes; Aedes; Animals; Arboviruses; Cellulose; Hydrogels; Insect Repellents; Mosquito Vectors; Nanoparticles; Piperidines; Zein; Zika Virus; Zika Virus Infection

After the latest dengue and Zika outbreaks, the fight against mosquito vectors has become an emerging area of research. One tool for this combat is repellents; however, these products are composed of different toxic agents. Botanical compounds with repellent potential are an alternative; however these compounds are highly volatile. Thus, the present study aimed to synthesize zein-based polymeric nanoparticles as an efficient carrier system for the sustained release of the repellents icaridin and geraniol and evaluate the toxicity of these nanorepellents comparing two different cell models. In vitro tests were carried out due to current Brazilian legislation prohibiting animal testing for cosmetics (current classification of repellents). The cytotoxicity and genotoxicity of the nanoparticles were evaluated in 2D and co-culture cell models (A549/lung epithelium, HaCaT/keratinocytes, HT-29/intestinal epithelium, and THP-1/peripheral blood monocytes). Cell viability by mitochondrial activity, cell membrane integrity, damage to genetic material, and expression of genes involved in the allergic/inflammatory system were evaluated. The results of cytotoxicity evaluation showed cell viability above 70% in both cell models. No differences were observed in genotoxicity assessment between cells exposed to nanorepellents and controls. In contrast, gene expression analysis showed increased cytokine expression for the emulsion compounds in 2D cell cultures compared to co-cultures. These findings open perspectives that zein-based nanorepellents have potential applications due to the reduced toxicity observed when the compounds are encapsulated and emerge as an alternative for arbovirus control. In addition, the study demonstrated that depending on the analysis, different results might be observed when comparing 2D and co-culture cell models to evaluate the toxicity of new nanosystems.

Topics: Acyclic Monoterpenes; Animals; Cell Culture Techniques; Coculture Techniques; Insect Repellents; Nanoparticles; Piperidines; Zein; Zika Virus; Zika Virus Infection

Repellents are among the leading products used against diseases transmitted by the Aedes aegypti mosquito. However, their indiscriminate use or high concentrations can cause severe adverse reactions, particularly in children and pregnant women. To protect them, nanotechnology is a promising tool to encapsulate active compounds against degradation, increase their effectiveness, and decrease their toxicity, as it can promote the modified release of the active compound. This study aimed to develop polymeric nanocapsules containing the repellent actives geraniol and icaridin using low concentrations of the active component, with the objective of promoting effective activity and greater safety against adverse reactions. The nanocapsules were developed by the interfacial deposition method, and the physicochemical properties of the nanocapsules were evaluated using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), zeta potential, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), release kinetics assay, and mathematical modeling. Cell viability was assessed by the MTT assay and genotoxicity analysis using the comet assay. The developed nanocapsules containing geraniol and icaridin showed mean diameters of 260 nm and 314 nm, respectively, with a polydispersity index < 0.2. The nanocapsules showed encapsulation efficiency values of 73.7 ± 0.1% for icaridin and 98.7 ± 0.1% for geraniol. Morphological analysis showed spherical nanocapsules with low polydispersity. The kinetic parameters calculated using the Korsmeyer−Peppas model indicated an anomalous release profile. Cell viability and genotoxicity analyses showed that the nanocapsules did not alter cell viability or damage DNA. The results demonstrate a promising nanostructured system with good physicochemical characteristics and good stability, with repellent activity against Aedes aegypti.

Topics: Acyclic Monoterpenes; Aedes; Animals; Child; Female; Humans; Insect Repellents; Nanocapsules; Piperidines; Polymers; Pregnancy

The shortage of geranylgeranyl-pyrophosphate (GGPP) was associated to an increased IL-1β release in the autoinflammatory syndrome mevalonate kinase deficiency (MKD), a rare inherited disease that has no specific therapy. Farnesyltransferase inhibitors (FTIs) act at the end of mevalonate pathway. Two FTIs, tipifarnib (Tip) and lonafarnib (Lon), were therefore evaluated as possible therapeutical choices for the treatment of MKD. FTIs could lead to a redirection of the limited available number of mevalonate intermediates preferentially to GGPP synthesis, eventually preventing the uncontrolled inflammatory response. The effect of Tip and Lon on intracellular cholesterol level (ICL) and on proinflammatory cytokines secretion was evaluated in a cellular model of MKD, chemically obtained treating RAW 264.7 cells with lovastatin (Lova) and alendronate (Ald). The combination of FTIs with the isoprenoid geraniol (GOH) was also tested both in this model and in monocytes isolated from MKD patients. Tip and Lon proved to revert the ICL lowering and to significantly reduce the lipopolysaccharide-induced cytokines secretion in Ald-Lova -RAW 264.7 cells. This anti-inflammatory effect was amplified combining the use of GOH with FTIs. The effect of GOH and Tip was successfully replicated in MKD patients' monocytes. Tip and Lon showed a dramatic anti-inflammatory effect in monocytes where mevalonate pathway was chemically or genetically impaired.

Topics: Acyclic Monoterpenes; Alendronate; Animals; Anti-Inflammatory Agents; Cell Line; Child; Child, Preschool; Cholesterol; Cytokines; Dose-Response Relationship, Drug; Enzyme Inhibitors; Farnesyltranstransferase; Humans; Inflammation Mediators; Lovastatin; Male; Mevalonate Kinase Deficiency; Mice; Monocytes; Phosphotransferases (Alcohol Group Acceptor); Piperidines; Polyenes; Polyisoprenyl Phosphates; Polyunsaturated Alkamides; Pyridines; Quinolones; Terpenes