Larvicidal Effect of Hyptis suaveolens (L.) Poit. Essential Oil Nanoemulsion on Culex quinquefasciatus (Diptera: Culicidae).

Mosquitoes can be vectors of pathogens and transmit diseases to both animals and humans. Species of the genus Culex are part of the cycle of neglected diseases, especially Culex quinquefasciatus, which is an anthropophilic vector of lymphatic filariasis. Natural products can be an alternative to synthetic insecticides for vector control; however, the main issue is the poor water availability of some compounds from plant origin. In this context, nanoemulsions are kinetic stable delivery systems of great interest for lipophilic substances. The objective of this study was to investigate the larvicidal activity of the Hyptis suaveolens essential oil nanoemulsion on Cx. quinquefasciatus. The essential oil showed a predominance of monoterpenes with retention time (RT) lower than 15 min. The average size diameter of the emulsions (sorbitan monooleate/polysorbate 20) was ≤ 200 nm. The nanoemulsion showed high larvicidal activity in concentrations of 250 and 125 ppm. CL50 values were 102.41 (77.5253−149.14) ppm and 70.8105 (44.5282−109.811) ppm after 24 and 48 h, respectively. The mortality rate in the surfactant control was lower than 9%. Scanning micrograph images showed changes in the larvae's integument. This study achieved an active nanoemulsion on Cx. quinquefasciatus through a low-energy-input technique and without using potentially toxic organic solvents. Therefore, it expands the scope of possible applications of H. suaveolens essential oil in the production of high-added-value nanosystems for tropical disease vector control.

Current Applications of Plant-Based Drug Delivery Nano Systems for Leishmaniasis Treatment.

Leishmania is a trypanosomatid that causes leishmaniasis. It is transmitted to vertebrate hosts during the blood meal of phlebotomine sandflies. The clinical manifestations of the disease are associated with several factors, such as the Leishmania species, virulence and pathogenicity, the host-parasite relationship, and the host's immune system. Although its causative agents have been known and studied for decades, there have been few advances in the chemotherapy of leishmaniasis. The urgency of more selective and less toxic alternatives for the treatment of leishmaniasis leads to research focused on the study of new pharmaceuticals, improvement of existing drugs, and new routes of drug administration. Natural resources of plant origin are promising sources of bioactive substances, and the use of ethnopharmacology and folk medicine leads to interest in studying new medications from phytocomplexes. However, the intrinsic low water solubility of plant derivatives is an obstacle to developing a therapeutic product. Nanotechnology could help overcome these obstacles by improving the availability of common substances in water. To contribute to this scenario, this article provides a review of nanocarriers developed for delivering plant-extracted compounds to treat clinical forms of leishmaniasis and critically analyzing them and pointing out the future perspectives for their application.

Potential Implications of Vouacapan Compounds for Insecticidal Activity: An In Silico Study.

BACKGROUND: From the fruits and seeds of the species of Pterodon, it is possible to obtain two main products: essential oil and oleoresin. In oleoresin, numerous vouacapan compounds have been demonstrated to have biological potential, including insecticidal activity. OBJECTIVE: In silico studies were performed to identify potential candidates for natural insecticides among the vouacapans present in the genus Pterodon. MATERIALS AND METHODS: Molecular docking and molecular dynamics studies were performed to analyze the interaction of vouacapan compounds with acetylcholinesterase of Drosophila melanogaster. Pharmacokinetic parameters regarding physicochemical properties, plasma protein binding, and activity in the central nervous system were evaluated. The toxicological properties of the selected molecules were predicted using malathion as the reference compound. RESULTS: 6α,7ß-dimethoxivouacapan-17-ene (15) showed a high number of interactions and scores in molecular docking studies. These results suggested that this compound exhibits an inhibitory activity of the enzyme acetylcholinesterase. This compound showed the best results regarding physicochemical properties, besides presenting low cutaneous permeability values, suggesting null absorption. Molecular dynamics studies demonstrated few conformational changes in the structure of the complex formed by compound 4 and acetylcholinesterase enzyme throughout the simulation time. CONCLUSION: It was determined that compound 4 (vouacapan 6α,7ß,17ß,19-tetraol) could be an excellent candidate for usage as a natural insecticide.

Efficacy of nanoemulsion with Pterodon emarginatus Vogel oleoresin for topical treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resistance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge. Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intraperitoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histopathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis.

A herbal oil in water nano-emulsion prepared through an ecofriendly approach affects two tropical disease vectors

ABSTRACT Lippia alba (Mill.) N.E.Br. ex Britton & P. Wilson, Verbenaceae, is considered a great source of a bioactive volatile oil. Due to the wide range of known chemotypes, its chemical analysis is very important. Among the several activities of this volatile oil, a potential larvicidal action against Culicidae species is highlighted. However, the low water miscibility of volatile oils limits their application in aqueous media. Oil in water nano-emulsions are in the spotlight of novelty to solve this main problem. Thus, the aim of the present study was to obtain this nanostructured system with L. alba volatile oil (citral chemotype) and evaluate its larvicidal activity against Aedes aegypti and Culex quinquefasciatus larvae. The major compounds were geranial (30.02%) and neral (25.26%). Low mean droplet size (117.0 ± 1.0 nm) and low polydispersity index (0.231 ± 0.004) were observed and no major changes were observed after seven days of storage. LC50 values against C. quinquefasciatus and A. aegypti third-instar larvae were respectively 38.22 and 31.02 ppm, while LC90 values were, respectively, 59.42 and 47.19 ppm. The present study makes use of a low energy, solvent-free and ecofriendly method with reduced costs. Thus, this paper contributes significantly to phyto-nanobiotechnology of larvicidal agents, opening perspectives for the utilization of L. alba volatile oil in integrated practices of vector control.

Preparation of aqueous nanodispersions with annatto (Bixa orellana L.) extract using an organic solvent-free and low energy method.

The seeds of Bixa orellana L. is widely used in food industry as a natural colorant. A major technological challenge for its utilization on aqueous food products is the low water solubility. Therefore, the present study aimed to obtain aqueous nanodispersions using this natural raw material by using a simple organic solvent-free and low energy method. Bixin and geranylgeraniol were found on the extract. The nanodispersions were prepared by addition of water on a mixture of extract and surfactant (s). The effect of the surfactants and dilution on the nanodispersions were also evaluated. Best results were achieved using polysorbate 80/sorbitan monooleate (HLB 13) (diluted in water, 1:10). The results shows the potential of this ecofriendly approach, in contrast to common methods that make use of potentially toxic organic solvents and high input of energy, which elevate the costs for further industrialization.

Preparation of a Nanoemulsion with Carapa guianensis Aublet (Meliaceae) Oil by a Low-Energy/Solvent-Free Method and Evaluation of Its Preliminary Residual Larvicidal Activity.

Andiroba (Carapa guianensis) seeds are the source of an oil with a wide range of biological activities and ethnopharmacological uses. However, few studies have devoted attention to innovative formulations, including nanoemulsions. The present study aimed to obtain a colloidal system with the andiroba oil using a low-energy and organic-solvent-free method. Moreover, the preliminary residual larvicidal activity of the nanoemulsion against Aedes aegypti was evaluated. Oleic and palmitic acids were the major fatty acids, in addition to the phytosterol ß-sitosterol and limonoids (tetranortriterpenoids). The required hydrophile-lipophile was around 11.0 and the optimal nanoemulsion was obtained using polysorbate 85. The particle size distribution suggested the presence of small droplets (mean diameter around 150 nm) and low polydispersity index (around 0.150). The effect of temperature on particle size distribution revealed that no major droplet size increase occurred. The preliminary residual larvicidal assay suggested that the mortality increased as a function of time. The present study allowed achievement of a potential bioactive oil in water nanoemulsion that may be a promising controlled release system. Moreover, the ecofriendly approach involved in the preparation associated with the great bioactive potential of C. guianensis makes this nanoemulsion very promising for valorization of this Amazon raw material.

Utilization of dynamic light scattering to evaluate Pterodon emarginatus oleoresin-based nanoemulsion formation by non-heating and solvent-free method

Abstract Pterodon emarginatus Vogel, Fabaceae, is a great source of bioactive compounds. The most known and studied herbal derivative from this species is an ambar-colored oleoresin that contains vouacapane diterpenes and volatile terpenoids, such as β-caryophyllene. Some recent papers aimed to generate nanoemulsions using this oleoresin for biological applications. However, they used high-energy methods that elevate costs of the process or heating procedures, which offer the disadvantage of possible volatile substances loss. Thus, as part of our ongoing studies with nanobiotechnology of natural products, especially regarding preparation of nanoemulsions with promising plant-based oils by low cost and low energy methods, we decided to evaluate the ability of non-heating and solvent-free method to generate P. emarginatus oleoresin-based nanoemulsions. Two non-ionic surfactants were used to generate the nanoemulsions by a simple homogenization method with vortex stirrer. Low mean droplet size (<180 nm) and low polydispersity index (<0.200) were observed even after one day of preparation. The low coefficient of variation for the analyzed parameters of different batches and similar profile for droplet size distribution suggested reproducibility of the method. After 30 days, some degree of droplet growth was observed on nanoemulsion prepared with polyethyleneglycol 400 monooleate, while almost no alteration was observed for nanoemulsion prepared with polysorbate 85. Programmed temperature ramp analysis revealed that no major effects on droplet size and polydispersity index were observed, suggesting the robustness of formed nanoemulsions. Thus, the present study shows for the first time the formation of sucupira-based nanoemulsions by a simple, low cost and ecofriendly method. This study opens new perspectives for bioactive evaluation of this novel nano-product.

Pterodon emarginatus oleoresin-based nanoemulsion as a promising tool for Culex quinquefasciatus (Diptera: Culicidae) control.

BACKGROUND: Preparation of nanoformulations using natural products as bioactive substances is considered very promising for innovative larvicidal agents. On this context, oil in water nanoemulsions develop a main role, since they satisfactorily disperse poor-water soluble substances, such as herbal oils, in aqueous media. Pterodon emarginatus, popularly known as sucupira, has a promising bioactive oleoresin. However, to our knowledge, no previous studies were carried out to evaluate its potential against Culex quinquefasciatus, the main vector of the tropical neglected disease called lymphatic filariasis or elephantiasis. Thus, we aimed to investigate influence of different pairs of surfactants in nanoemulsion formation and investigate if a sucupira oleoresin-based nanoemulsion has promising larvicidal activity against this C. quinquefasciatus. We also evaluated morphological alteration, possible mechanism of insecticidal action and ecotoxicity of the nanoemulsion against a non-target organism. RESULTS: Among the different pairs of surfactants that were tested, nanoemulsions obtained with polysorbate 80/sorbitan monooleate and polysorbate 80/sorbitan trioleate presented smallest mean droplet size just afterwards preparation, respectively 151.0 ± 2.252 and 160.7 ± 1.493 nm. They presented high negative zeta potential values, low polydispersity index (<0.300) and did not present great alteration in mean droplet size and polydispersity index after 1 day of preparation. Overall, nanoemulsion prepared with polysorbate 80/sorbitan monooleate was considered more stable and was chosen for biological assays. It presented low LC50 value against larvae (34.75; 7.31-51.86 mg/L) after 48 h of treatment and some morphological alteration was observed. The nanoemulsion did not inhibit acetylcholinesterase of C. quinquefasciatus larvae. It was not toxic to green algae Chlorella vulgaris at low concentration (25 mg/L). CONCLUSIONS: Our results suggest that optimal nanoemulsions may be prepared with different surfactants using a low cost and low energy simple method. Moreover, this prototype proved to be effective against C. quinquefasciatus, being considered an ecofriendly novel nanoproduct that can be useful in integrated control programs of vector control.

Development of a Larvicidal Nanoemulsion with Pterodon emarginatus Vogel Oil.

Pterodon emarginatus Vogel is a Brazilian species that belongs to the family Fabaceae, popularly known as sucupira. Its oil has several biological activities, including potent larvicidal property against Aedes aegypti. This insect is the vector of dengue, a tropical disease that has been considered a critical health problem in developing countries, such as Brazil. Most of dengue control methods involve larvicidal agents suspended or diluted in water and making active lipophilic natural products available is therefore considered a technological challenge. In this context, nanoemulsions appear as viable alternatives to solve this major problem. The present study describes the development of a novel nanoemulsion with larvicidal activity against A. aegypti along with the required Hydrophile Lipophile Balance determination of this oil. It was suggested that the mechanism of action might involve reversible inhibition of acetylcholinesterase and our results also suggest that the P. emarginatus nanoemulsion is not toxic for mammals. Thus, it contributes significantly to alternative integrative practices of dengue control, as well as to develop sucupira based nanoproducts for application in aqueous media.