Polymeric nanoparticles loaded with the 3,5,3´-triiodothyroacetic acid (Triac), a thyroid hormone: factorial design, characterization, and release kinetics

Karen C dos Santos,1 Maria Fatima GF da Silva,1 Edenir R Pereira-Filho,1 Joao B Fernandes,1 Igor Polikarpov,2 Moacir R Forim11Department of Chemistry, Federal University of Sao Carlos, Sao Carlos, 2Physics Institute of Sao Carlos, University of Sao Paulo, Sao Carlos, Sao Paulo, BrazilAbstract: This present investigation deals with the development and optimization of polymeric nanoparticle systems loaded with 3,5,3´-triiodothyroacetic acid (Triac). A 211–6 fractional factorial design and another 22 factorial design were used to study the contrasts on particle size distribution, morphology, surface charge, drug content, entrapment efficiency, and in vitro drug release profiles. The independent variables were the concentration of Triac, type and quantity of both polymer and oil, quantity of Span™ 60 and Tween® 80, volume of solvent and water, and velocity of both magnetic stirring and the transfer of the organic phase into the aqueous solution. The results of optimized formulations showed a narrow size distribution with a polydispersity index lower than 0.200. The particle sizes were on average 159.6 nm and 285.6 nm for nanospheres and nanocapsules, respectively. The zeta potential was higher than 20 mV (in module) and the entrapment efficiency was nearly 100%. A high-performance liquid chromatography method was developed, validated, and efficiently applied to Triac quantification in colloidal suspension. The main independent variables were the type and quantity of the polymer and oil. In vitro drug release profile depicted several features to sustain Triac release. Different formulations showed various release rates indicating an interaction between Triac and other formulation compounds such as polymer and/or oil quantity. Two different models were identified (biexponential and monoexponential) that allowed the control of both the release rate and Triac concentration. Thus, the prepared nanoparticles described here may be of clinical importance in delivering Triac for thyroid treatment.Keywords: Triac, nanoparticles, optimization, factorial design of experiments, HPLC analytical metho

N-Acetylcysteine in Agriculture, a Novel Use for an Old Molecule: Focus on Controlling the Plant-Pathogen Xylella fastidiosa

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Xylella fastidiosa is a plant pathogen bacterium that causes diseases in many different crops. In citrus, it causes Citrus Variegated Chlorosis (CVC). The mechanism of pathogenicity of this bacterium is associated with its capacity to colonize and form a biofilm in the xylem vessels of host plants, and there is not yet any method to directly reduce populations of this pathogen in the field. In this study, we investigated the inhibitory effect of N-Acetylcysteine (NAC), a cysteine analogue used mainly to treat human diseases, on X. fastidiosa in different experimental conditions. Concentrations of NAC over 1 mg/mL reduced bacterial adhesion to glass surfaces, biofilm formation and the amount of exopolysaccharides (EPS). The minimal inhibitory concentration of NAC was 6 mg/mL. NAC was supplied to X. fastidiosa-infected plants in hydroponics, fertigation, and adsorbed to organic fertilizer (NAC-Fertilizer). HPLC analysis indicated that plants absorbed NAC at concentrations of 0.48 and 2.4 mg/mL but not at 6 mg/mL. Sweet orange plants with CVC symptoms treated with NAC (0.48 and 2.4 mg/mL) in hydroponics showed clear symptom remission and reduction in bacterial population, as analyzed by quantitative PCR and bacterial isolation. Experiments using fertigation and NAC-Fertilizer were done to simulate a condition closer to that normally is used in the field. For both, significant symptom remission and a reduced bacterial growth rate were observed. Using NAC-Fertilizer the lag for resurgence of symptoms on leaves after interruption of the treatment increased to around eight months. This is the first report of the anti-bacterial effect of NAC against a phytopathogenic bacterium. The results obtained in this work together with the characteristics of this molecule indicate that the use of NAC in agriculture might be a new and sustainable strategy for controlling plant pathogenic bacteria.88Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [2008/51274-5, 471448/2011-7, INCT-Citros 08/57909-2, 573848/08-4

Valorization of Hesperidin from Citrus Residues: Evaluation of Microwave-Assisted Synthesis of Hesperidin-Mg Complex and Their Insecticidal Activity

The aim of the current study was the valorization of hesperidin, the dominant flavonoid in citrus processing waste, by microwave-assisted synthesis of hesperidin-Mg complex, improving its antioxidant activity and insecticidal potential. Here we show, for the first time, that microwaveassisted synthesis of [Mg(hesp)2(phen)]OAc (1) (hesp: hesperidin, phen: phenanthroline) improve the reaction rate and yield. The nuclear magnetic resonance (NMR) experiments proved to be powerful tools for the identification of three isomers in metal complexes. Moreover, we explore the insecticidal potential of 1 and [Mg(phen)2(Isov)]OAc (2) (Isov : isovanillic acid) complexes against three insects. Complex 1 killed 80% of adults whitefly at 0.14 μmol L-1, and 2 76% at 0.36 μmol L-1. There was a total mortality of Spodoptera frugiperda with 2 at 0.39 μmol L-1, and 83% with 1 at 0.14 μmol L-1. Both have similar activity, and represent a novel group of insecticide for Bemisia tabaci and S. frugiperda; nevertheless, the benefits of both as Myzus persicae repellent require further evaluation

Effectiveness of two biopesticides against the invasive tomato pest Tuta absoluta

International audienceTuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) is among the most devastating pests worldwide of solanaceous plants, particularly of tomato (Solanum lycopersicum L.). Since its recent introduction into sub-Saharan Africa, it has become an additional widespread tomato pest throughout the region. When no control measures are taken, yield losses caused by T. absoluta larvae can reach 100%. Chemical control remains the primary management option despite its many adverse effects and increasing inefficiency due to the species' endophytic habits and ability to develop insecticide resistance. Safer and more effective alternatives are therefore urgently required. Here, we investigated the effectiveness of two bioinsecticides compared to that of a widely used deltamethrin-based synthetic insecticide, in preventing damage caused by T. absoluta larvae to tomato leaves and fruits, thereby affecting tomato yield. A field trial was conducted in 2018 and 2019 in northwestern Senegal using a randomized complete block design. Damage caused by T. absoluta affected approximately 65% of total leaf area and 3-24% of the fruits. Damage to the leaves caused by other insect species or other factors was less significant. At the dose applied, the chemical insecticide did not significantly reduce the surface area of leaflets affected by T. absoluta or other causal agents, the number of T. absoluta mines on the leaflets, or the proportion of fruits damaged. In contrast, the azadirachtin and Bacillus thuringiensis (Bt) formulations rapidly and significantly reduced damage to both leaves and fruits. The proportion of fruits damaged was reduced by a factor two and the total tomato yield was improved, particularly when the Bt formulation was used. In addition to their effectiveness in reducing damage caused by T. absoluta larvae to tomato leaves and fruit, and increasing the yield of marketable fruits, the viability of these organic alternatives was shown. The scope of our results is discussed in the context of T. absoluta control, in particular in integrated pest management programmes for tomato crops