Larvicidal properties of terpenoid-based nanoemulsions against the dengue vector Aedes aegypti L. and their potential toxicity against non-target organism.

The development of insecticide resistance in mosquitoes of public health importance has encouraged extensive research into innovative vector control methods. Terpenes are the largest among Plants Secondary Metabolites and have been increasingly studied for their potential as insecticidal control agents. Although promising, terpenes are insoluble in water, and they show low residual life which limits their application for vector control. In this study, we developed and evaluated the performances of terpenoid-based nanoemulsions (TNEs) containing myrcene and p-cymene against the dengue vector Aedes aegypti and investigated their potential toxicity against non-target organisms. Our results showed that myrcene and p-cymene showed moderate larvicidal activity against mosquito larvae compared to temephos an organophosphate widely used for mosquito control. However, we showed similar efficacy of TNEs against both susceptible and highly insecticide-resistant mosquitoes from French Guyana, hence suggesting an absence of cross-resistance with conventional insecticides. We also showed that TNEs remained effective for up to 45 days in laboratory conditions. The exposure of zebrafish to TNEs triggered behavioral changes in the fish at high doses but they did not alter the normal functioning of zebrafish organs, suggesting a good tolerability of non-target organisms to these molecules. Overall, this study provides new insights into the insecticidal properties and toxicity of terpenes and terpenoid-based formulations and confirms that TNE may offer interesting prospects for mosquito control as part of integrated vector management

Residual activity of Cym-NE and Myr-NE against susceptible larvae of <i>Ae</i>. <i>Aegypti</i>. numbers in the bars represent the sample size tested.

Residual activity of Cym-NE and Myr-NE against susceptible larvae of Ae. Aegypti. numbers in the bars represent the sample size tested.</p

Composition of the monoterpenes nanoemulsions.

The development of insecticide resistance in mosquitoes of public health importance has encouraged extensive research into innovative vector control methods. Terpenes are the largest among Plants Secondary Metabolites and have been increasingly studied for their potential as insecticidal control agents. Although promising, terpenes are insoluble in water, and they show low residual life which limits their application for vector control. In this study, we developed and evaluated the performances of terpenoid-based nanoemulsions (TNEs) containing myrcene and p-cymene against the dengue vector Aedes aegypti and investigated their potential toxicity against non-target organisms. Our results showed that myrcene and p-cymene showed moderate larvicidal activity against mosquito larvae compared to temephos an organophosphate widely used for mosquito control. However, we showed similar efficacy of TNEs against both susceptible and highly insecticide-resistant mosquitoes from French Guyana, hence suggesting an absence of cross-resistance with conventional insecticides. We also showed that TNEs remained effective for up to 45 days in laboratory conditions. The exposure of zebrafish to TNEs triggered behavioral changes in the fish at high doses but they did not alter the normal functioning of zebrafish organs, suggesting a good tolerability of non-target organisms to these molecules. Overall, this study provides new insights into the insecticidal properties and toxicity of terpenes and terpenoid-based formulations and confirms that TNE may offer interesting prospects for mosquito control as part of integrated vector management.</div

Effect of oral treatment with Cym-NE and Myr-NE and control (water) over zebrafish behavior changes assessed in three stages.

Effect of oral treatment with Cym-NE and Myr-NE and control (water) over zebrafish behavior changes assessed in three stages.</p

Larvicidal activity of monoterpenes, free and in nanoemulsions against insecticide-resistant <i>Ae</i>. <i>aegypti</i> (Guyana strain) after 24 hours of exposure, using the WHO larval bioassay.

Larvicidal activity of monoterpenes, free and in nanoemulsions against insecticide-resistant Ae. aegypti (Guyana strain) after 24 hours of exposure, using the WHO larval bioassay.</p

Fig 1 -

Concentration-response plots of terpenes against Ae. Aegypti larvae: A–Bora strain with Cym and Cym-NE; B–Bora strain with Myr and Myr-NE; C–Guyana strain with Cym and Cym-Ne and D–Guyana strain with Myr and My-NE.</p

Fig 4 -

Histopathological changes observed in the intestine (A and B), liver (Cand D) and kidneys (E and F). In A and B intestinal tissue with caliciform cells (CC), villi (V), Muscle layer (ML), villi degeneration (VD) and caliciform cell hyperplasia (CCHP); In C and D normal hepatocytes (H), Cytoplasmatic vacuolization (CV), nuclear atrophy (NA); In E and F tubules (Tb), Lymphoid tissue (LT), Increase in tubular lumen (ITL), mild tubular hyaline degeneration (THD). H&E staining, IHC in the intestine (G), liver (H) and kidneys (I) of adult zebrafish in the acute oral toxicity test performed using Ne-Cym (1750 e 2000 mg/kg) e Ne-Myr (2000 mg/kg). Data show the mean ± SD (n = 5/group). Statistical analysis was performed through one-way ANOVA followed by the post hoc Tukey test.</p

Fig 2 -

Concentrations effect curves of the combination of A—Myrcene:p-cymene (1:1) and B -Myr-NE:Cym-NE (1:1) and Interaction curves between C—Myrcene:p-cymene (1:1) and D -Myr-NE:Cym-NE (1:1).</p

Larvicidal activity of monoterpenes, free and in nanoemulsions, against <i>Ae</i>. <i>aegypti</i> L. (Bora strain) after 24 hours of exposure using the WHO larval bioassay.

Larvicidal activity of monoterpenes, free and in nanoemulsions, against Ae. aegypti L. (Bora strain) after 24 hours of exposure using the WHO larval bioassay.</p

Targeted Liposomes: A Nonviral Gene Delivery System for Cancer Therapy

Cancer is the second most frequent cause of death worldwide, with 28.4 million new cases expected for 2040. Despite de advances in the treatment, it remains a challenge because of the tumor heterogenicity and the increase in multidrug resistance mechanisms. Thus, gene therapy has been a potential therapeutic approach owing to its ability to introduce, silence, or change the content of the human genetic code for inhibiting tumor progression, angiogenesis, and metastasis. For the proper delivery of genes to tumor cells, it requires the use of gene vectors for protecting the therapeutic gene and transporting it into cells. Among these vectors, liposomes have been the nonviral vector most used because of their low immunogenicity and low toxicity. Furthermore, this nanosystem can have its surface modified with ligands (e.g., antibodies, peptides, aptamers, folic acid, carbohydrates, and others) that can be recognized with high specificity and affinity by receptor overexpressed in tumor cells, increasing the selective delivery of genes to tumors. In this context, the present review address and discuss the main targeting ligands used to functionalize liposomes for improving gene delivery with potential application in cancer treatment