New weapons against the disease vector Aedes aegypti: From natural products to nanoparticles.

Despite the global burden of viral diseases transmitted by Aedes aegypti, there is a lack of effective means of prevention and treatment. Strategies for vector control include chemical and biological approaches such as organophosphates and Bacillus thuringiensis var. israelensis (Bti), among others. However, important concerns are associated, such as resistance in mosquito larvae and deleterious effects on non-target organisms. In this scenario, novel approaches against A. aegypti have been investigated, including natural products (e.g. vegetable oil and extracts) and nanostructured systems. This review focuses on potential strategies for fighting A. aegypti, highlighting plant-based materials and nanomaterials able to induce toxic effects on egg, larva, pupa and adult mosquitoes. Issues including aspects of conventional vector control strategies are presented, and finally new insights on development of eco-friendly nanoformulations against A. aegypti are discussed.

Conventional and PEGylated Liposomes as Vehicles of Copaifera sabulicola.

Traditional medicine uses resin oils extracted from plants of the genus Copaifera for several purposes. Resin oils are being studied to understand and profile their pharmacological properties. The aim of this work was to prepare and to characterize conventional and pegylated liposomes incorporating resin oils or the hexanic extract obtained from Copaifera sabulicola (copaiba) leaves. The cytotoxic effect of these products was also investigated. Conventional and stealth liposomes with copaiba extract showed similar average diameters (around 126 nm), encapsulation efficiencies greater than 75% and were stable for 90 days. A cytotoxicity test was performed on murine glioma cells and the developed liposomes presented antiproliferative action against these cancer cells at the average concentration of 30 µg/mL. Phytochemicals encapsulated in PEGylated liposomes induced greater reduction in the viability of tumor cells. In addition, bioassay-s measured the cytotoxicity of copaiba resin oil (Copaifera sabulicola) in liposomes (conventional and PEGylated), which was also checked against pheochromocytoma PC12 cells. Its safety was verified in normal rat astrocytes. The results indicate that liposomes encapsulating copaiba oil showed cytotoxic activity against the studied tumor strains in a dose-dependent fashion, demonstrating their potential applications as a chemotherapeutic bioactive formulation.

Biopesticide Encapsulation Using Supercritical CO2: A Comprehensive Review and Potential Applications.

As an alternative to synthetic pesticides, natural chemistries from living organisms, are not harmful to nontarget organisms and the environment, can be used as biopesticides, nontarget. However, to reduce the reactivity of active ingredients, avoid undesired reactions, protect from physical stress, and control or lower the release rate, encapsulation processes can be applied to biopesticides. In this review, the advantages and disadvantages of the most common encapsulation processes for biopesticides are discussed. The use of supercritical fluid technology (SFT), mainly carbon dioxide (CO2), to encapsulate biopesticides is highlighted, as they reduce the use of organic solvents, have simpler separation processes, and achieve high-purity particles. This review also presents challenges to be surpassed and the lack of application of SFT for biopesticides in the published literature is discussed to evaluate its potential and prospects.

Development of membranes based on carboxymethyl cellulose/acetylated arrowroot starch containing bromelain extract carried on nanoparticles and liposomes.

Polymeric membranes have been used in several applications, including their use as curatives in cutaneous wounds. Bromelain has long been used for anti-inflammatory purposes, so the objective of this work was to produce carboxymethylcellulose-acetylated blends, incorporate bromelain, characterize the systems, compare the blends with bromelain loaded in nanoparticles and liposomes and, finally, to evaluate their healing potential. Four membrane formulations were produced by solvent evaporation: the control, membranes containing free bromelain, bromelain-loaded nanoparticles (NPs) and bromelain-loaded liposomes (LIPs). The enzyme concentration was the same for all formulations. Transparent, flexible and intact films were obtained. The membranes containing free bromelain, bromelain-loaded NPs and bromelain-loaded LIPs had higher water content, lower water vapor permeability and maximum tensile strength, and greater elongation at rupture. The capacity to absorb simulated exudate was higher in samples containing free bromelain, and bioadhesion was reduced in the presence of free bromelain compared to the control. An in vivo assay was performed to verify the membranes' healing potential. Histological analysis revealed no edema on the 14th day in animals treated with membranes containing bromelain-loaded NPs and LIPs.

Bioactive compounds of Copaifera sp. impregnated into three-dimensional gelatin dressings.

This study investigates the immersion impregnation process of the copaiba oleoresin and leaf extract into SpongostanTM gelatin dressings to be used in wound healing treatment. Copaiba oleoresin and leaf extract were characterized by spectroscopic analyses in order to confirm the identity of bioactive compounds and their compatibility with dressing material. Their antibacterial properties were evaluated and oleoresin activity against Escherichia coli and Staphylococcus aureus bacteria was confirmed while the leaf extract showed activity against S. aureus. Solubility assays in organic solvents revealed that copaiba oleoresin is miscible into dichloromethane, while leaf extract showed a 20 g/ml solubility coefficient at 35 °C in the same solvent. These miscibility and solubility conditions were selected for the impregnation process. Using the organic solvent immersion method, 11 mg of copaiba oleoresin and 19 mg of leaf extract were impregnated into 1 cm3 of 3D matrix. The main bioactives from copaiba products, such as ß-caryophyllene and lupeol, were tracked in the gelatin dressing. DSC and TGA assays showed no thermal changes in the samples after impregnation. Furthermore, the spatial organization of foam structure of the dressings was preserved after superficial distribution of oleoresin, as well as amorphous-like particulate deposition of leaf extract. The main compound of copaiba oleoresin, ß-caryophyllene, which exhibits well-known anti-inflammatory activities, and the main compound of copaiba leaf extract, lupeol, also an anti-inflammatory agent, were successfully impregnated using organic solvent in wound dressings and are promising for further application on tissue wound healing. Graphical Abstract.

HDL Particle Size and Functionality Comparison between Patients with and without Confirmed Acute Myocardial Infarction.

INTRODUCTION: Cardiovascular diseases (CVDs) continue to be the most common cause of death worldwide, and acute myocardial infarction (AMI) is noteworthy due to its great magnitude. OBJECTIVES: This study was carried out to evaluate the structure (molecular and particle size) and functionality of high-density lipoprotein (HDL) shortly after AMI, in the presence of acute inflammatory response. CASUISTIC AND METHODS: A cross-sectional, observational study was conducted between January 2015 and August 2016, with a total convenient sample of 85 patients. The patients' data were segregated according to the Registry of Acute Myocardial Infarction (REAMI), with 45 confirmed AMI patients. The study groups consisted of patients from both sexes, older than 35 years, presented to the Hospital São Rafael (HSR) initially with AMI clinical symptoms. In addition, 40 nonischemic control patients (CPs), without AMI symptomatology, and according to previous inclusion criteria, were selected for convenience in an outpatient care unit. The HDL particle size was measured by laser light scattering (LLS), after separation of HDL from apoB-rich lipoproteins. The paraoxonase-1 (PON-1) activity was determined in a spectrophotometer by using paraoxon as a substrate. The other laboratory marker information, secondary data, was obtained in the laboratory system. RESULTS: The HDL particle size, free cholesterol, and hs-CRP analysis showed significant differences when compared between REAMI and CP groups (p < 0.0001, p=0.007, and p < 0.0001; two-tailed unpaired t-test, respectively). Regarding paraoxonase, the data comparison between REAMI and CP groups was also significantly different (p < 0.0067; two-tailed unpaired t-test). CONCLUSION: Despite an important current database on the HDL cholesterol role, our study provides relevant complementary information about the HDL particle susceptibility to the inflammation following AMI. The HDL particles' quantitative and functional attributes should be measured as markers of HDL functionality.

Use of polyhydroxybutyrate and ethyl cellulose for coating of urea granules.

Fertilizers contain essential nutrients for agricultural growth and development. However, most nitrogen fertilizers are substances with high solubility of ions and are very susceptible to leaching and volatilization. To minimize these losses, an alternative is the creation of a physical barrier around granules. One way is to coat granules with polymers. In the present work urea granules were coated with polyhydroxybutyrate and ethyl cellulose in various conditions in the presence of emulsifiers. The original granules and the final products were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and thermogravimetry, to evaluate the surface morphology, the interaction between the granules and the coating, and the rates of mass change. The rates of urea release in distilled water were measured with a commercial enzyme kit. It is shown that those polymers are effective for coating of granules, leading to reduction of rates of urea dissolution in water.

Characteristics of lipid micro- and nanoparticles based on supercritical formation for potential pharmaceutical application.

The interest of the pharmaceutical industry in lipid drug delivery systems due to their prolonged release profile, biocompatibility, reduction of side effects, and so on is already known. However, conventional methods of preparation of these structures for their use and production in the pharmaceutical industry are difficult since these methods are usually multi-step and involve high amount of organic solvent. Furthermore, some processes need extreme conditions, which can lead to an increase of heterogeneity of particle size and degradation of the drug. An alternative for drug delivery system production is the utilization of supercritical fluid technique. Lipid particles produced by supercritical fluid have shown different physicochemical properties in comparison to lipid particles produced by classical methods. Such particles have shown more physical stability and narrower size distribution. So, in this paper, a critical overview of supercritical fluid-based processes for the production of lipid micro- and nanoparticles is given and the most important characteristics of each process are highlighted.

Evaluation of thermal-oxidative stability and antiglioma activity of Zanthoxylum tingoassuiba essential oil entrapped into multi- and unilamellar liposomes.

Zanthoxylum tinguassuiba essential oil (ZtEO) contains α-bisabolol, a known antiglioma sesquiterpene, among other potentially active substances. Medical applications of this essential oil require advances in the design of distinctive carriers due to its low water solubility and easy degradation by heat, light, and oxygen. The aim of this work was to evaluate enhancement in oxidative stability and the ability to reduce glioblastoma cell viability of ZtEO loaded into liposomes. Multi- and unilamellar vesicles were prepared to carry ZtEO. By using thermal analysis, it was observed that thermal-oxidative stability of the liposomal ZtEO was enhanced, when compared to its free form. Liposomal ZtEO also presented significant apoptotic-inducing activity for glioma cells. These results show that liposomal systems carrying ZtEO may be a potential alternative for gliobastoma treatment.

Validation of a high-performance liquid chromatography method for the determination of (-)-alpha-bisabolol from particulate systems.

A reversed-phase high performance liquid chromatography method has been developed and validated for determination and quantitation of the natural sesquiterpene (-)-alpha-bisabolol. Furthermore the application of the method was done by characterization of chitosan milispheres and liposomes entrapping Zanthoxylum tingoassuiba essential oil, which contains appreciable amount of (-)-alpha-bisabolol. A reversed-phase C(18) column and gradient elution was used with the mobile phase composed of (A) acetonitrile-water-phosphoric acid (19:80:1) and (B) acetonitrile. The eluent was pumped at a flow rate of 0.8 mL/min with UV detection at 200 nm. In the range 0.02-0.64 mg/mL the assay showed good linearity (R(2 )= 0.9999) and specificity for successful identification and quantitation of (-)-alpha-bisabolol in the essential oil without interfering peaks. The method also showed good reproducibility, demonstrating inter-day and intra-day precision based on relative standard deviation values (up to 3.03%), accuracy (mean recovery of 100.69% +/- 1.05%) and low values of detection and quantitation limits (0.0005 and 0.0016 mg/mL, respectively). The method was also robust for showing a recovery of 98.81% under a change of solvent in standard solutions. The suitability of the method was demonstrated by the successful determination of association efficiency of the (-)-alpha-bisabolol in chitosan milispheres and liposomes.

Poly-lactide-co-glycolide microparticle sizes: a rational factorial design and surface response analysis.

Microsphere size is a primary determinant of solute release velocity. We present here a rational way for producing PLGA microspheres with different and controlled sizes. The following process variables were studied: Stirring velocity during the second emulsion step, dispersed and continuous phases volume ratio, and poly(vinyl alcohol) concentration in the continuous phase. A full factorial experimental design 2(3) with triplicate at the central point was used to determine the influence of variables on PLGA microsphere mean size. The stirring velocity and poly(vinyl alcohol) concentration were the main variables at 0.95 significance level. An influence of PVA and stirring velocity on microspheres size is observed, there is no correlation for DP/CP volume ratio on size of microspheres. By combining the two variables--the stirring velocity and poly(vinyl alcohol) concentration, the surface response was analyzed. The increase of poly(vinyl alcohol) concentration with concomitant increase on stirring velocity produced microspheres with the lower sized. In contrast the lower poly(vinyl alcohol) concentration and the lower stirring velocity used produced the higher microspheres sized. Uniformly spherical and smooth microspheres (4-15 microm of diameter) were obtained. No significant difference was observed on Ponca S loading within the experimental region. Our results open the possibility of formulating PLGA microspheres with custom sizes performing a minimum of experiments as required for specific applications.