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IntroductionOverusing and misusing pesticides, including paraquat (PQ), have led to numerous environmental contamination complications. PQ is an emerging bio-accumulative contaminant that is present in environmental aqueous matrices. Adsorption techniques are part of a set of technologies applied in ecological remediation, known for their high effectiveness in removing aqueous PQ. A study of the PQ adsorption capacity of three cyclodextrin–silica nanocomposites (α-CDSi, β-CDSi, and γ-CDSi) from contaminated waters is presented in this paper.MethodsThe cyclodextrin–silica nanocomposites were synthesized via an esterification reaction between the inorganic matrix and cyclodextrins (CDs) (α, β, and γ) and were characterized physicochemically by spectroscopic, thermal, and surface methods. Their PQ removal performance from contaminated aqueous media was studied under different experimental conditions.Results and DiscussionThe results showed a fast adsorptive response in removal treatment studies over time. Adsorption capacities of 87.22, 57.17, and 77.27 mg.g−1 were found for α-CDSi, β-CDSi, and γ-CDSi, respectively, at only 30 min of treatment. Thermodynamic studies indicated spontaneous and exothermic adsorption processes. The removal assays responded mainly to physisorption mechanisms with contributions from chemisorption mechanisms. Spectroscopic assays showed a strong interaction of PQ with the adsorbents used. Innovative CDSi nanocomposites have proven to be highly efficient in applying aqueous PQ remediation, thus proving to be sustainable adsorbents of contaminants of emerging importance worldwide.

To address the escalating global demand for food production, it is imperative to minimize agricultural losses caused by pests, accounting for up to 40 % of the substantial worldwide losses of 70 billion USD. While conventional pesticides raise environmental concerns, environmentally friendly alternatives like curcumin and carvacrol face low biological activity due to their low solubility and premature degradation in environmental conditions, that is, degradation can occur due to solar radiation, high temperature, etc., before the active ingredients can exert its full potential. This study introduces zein-based nanocarriers encapsulating curcumin and carvacrol, exhibiting favorable characteristics. Cytotoxicity tests indicate approximately 60% viability for fibroblast cell lines compared to 20% for keratinocyte cell lines. The nanoencapsulated compounds exhibit promising biological activity against soybean pests, mites, and caterpillars, without causing phytotoxicity. Tetranychus urticae mortality rates reach 77.1 ± 11.5 %, and nanoencapsulated ingredients demonstrate higher repellency (61.1 ± 8.8%) than emulsified ones (51.1 ± 5.4 %). Nanoencapsulated ingredients exhibit significantly higher mortality rates for Spodoptera cosmioides and Spodoptera eridania, underscoring the potential of nanoencapsulation in bolstering bioactivity against specific pests and promoting sustainable agricultural practices.

Lidocaine is the most commonly used local anesthetic worldwide, known for its rapid onset and moderate duration of anesthesia. However, it is short-lived and does not effectively promote effective topical anesthesia in the oral cavity when used alone. Our aim was to investigate whether an approximate 50% encapsulation of lidocaine in poly(ε-caprolactone) nanocapsules (LDC-Nano) would be able to increase its permeation and analgesic efficacy and reduce cytotoxicity. In this study, we characterized LDC-Nano and conducted MTT tests with HaCaT cells to assess their in vitro cytotoxicity. Additionally, in vitro permeation assays across the pig esophageal epithelium and the anesthetic efficacy of the hind paw incision model in rats were performed. Plain lidocaine (LDC) was compared with LDC-Nano and lidocaine hydrochloride plus epinephrine (LDC-Epi). The physicochemical characteristics of LDC-Nano were satisfactory (pH: 8.1 ± 0.21; polydispersity index: 0.08 ± 0.01; mean diameter (nm): 557.8 ± 22.7; and encapsulation efficiency (%): 51.8 ± 1.87) and remained stable for up to 4 months. LDC-Nano presented similar in vitro cytotoxicity to LDC but was higher than LDC-Epi (LD50: LDC = 0.48%; LDC-Nano = 0.47%; and LDC-Epi = 0.58%; p < 0.0001). Encapsulation increased the permeability coefficient about 6.6 times and about 7.5 the steady-state flux of lidocaine across the mucosal epithelium. Both encapsulation and epinephrine improved anesthesia duration, with epinephrine demonstrating superior efficacy (100% of animals were anesthetized up to 100, 30, and 20 min when LDC-Epi, LDC-nano, and LDC were used, respectively). Although LDC-Epi demonstrated superior in vivo anesthetic efficacy, the in vitro permeation and cytotoxicity of LDC-Nano indicate promising avenues for future research, particularly in exploring its potential application as a topical anesthetic in the oral cavity.

Abstract Dengue, yellow fever, Chinkungunya, Zika virus, and West Nile fever have infected millions and killed a considerable number of humans since their emergence. These arboviruses are transmitted by mosquito bites and topical chemical repellents are the most commonly used method to protect against vector arthropod species. This study aimed to develop a new generation of repellent formulations to promote improved arboviruses transmission control. A repellent system based on polycaprolactone (PCL)-polymeric nanoparticles was developed for the dual encapsulation of IR3535 and geraniol and further incorporation into a thermosensitive hydrogel. The physicochemical and morphological parameters of the prepared formulations were evaluated by dynamic light scattering (DLS), nano tracking analysis (NTA), atomic force microscopy (AFM). In vitro release mechanisms and permeation performance were evaluated before and after nanoparticles incorporation into the hydrogels. FTIR analysis was performed to evaluate the effect of formulation epidermal contact. Potential cytotoxicity was evaluated using the MTT reduction test and disc diffusion methods. The nanoparticle formulations were stable over 120 days with encapsulation efficiency (EE) of 60% and 99% for IR3535 and geraniol, respectively. AFM analysis revealed a spherical nanoparticle morphology. After 24 h, 7 ± 0.1% and 83 ± 2% of the GRL and IR3535, respectively, were released while the same formulation incorporated in poloxamer 407 hydrogel released 11 ± 0.9% and 29 ± 3% of the loaded GRL and IR3535, respectively. GRL permeation from PCL nanoparticles and PCL nanoparticles in the hydrogel showed similar profiles, while IR3535 permeation was modulated by formulation compositions. Differences in IR3535 permeated amounts were higher for PCL nanoparticles in the hydrogels (36.9 ± 1.1 mg/cm2) compared to the IR3535-PCL nanoparticles (29.2 ± 1.5 mg/cm2). However, both active permeation concentrations were low at 24 h, indicating that the formulations (PCL nanoparticles and PCL in hydrogel) controlled the bioactive percutaneous absorption. Minor changes in the stratum corneum (SC) caused by interaction with the formulations may not represent a consumer safety risk. The cytotoxicity results presented herein indicate the carrier systems based on poly-epsilon caprolactone (PCL) exhibited a reduced toxic effect when compared to emulsions, opening perspectives for these systems to be used as a tool to prolong protection times with lower active repellent concentrations.

Abstract Background Biogenic metallic nanoparticles have been emerging as a promising alternative for the control of phytopathogens and as nanofertilizers. In this way, it is essential to investigate the possible impacts of these new nanomaterials on plants. In this study, the effects of soil contamination with biogenic silver (AgNPs) and iron (FeNPs) with known antifungal potential were investigated on morphological, physiological and biochemical parameters of soybean seedlings. Results The exposure of plants/seedlings to AgNPs induced the reduction of root dry weight followed by oxidative stress in this organ, however, adaptive responses such as a decrease in stomatal conductance without impacts on photosynthesis and an increase in intrinsic water use efficiency were also observed. The seedlings exposed to FeNPs had shown an increase in the levels of oxygen peroxide in the leaves not accompanied by lipid peroxidation, and an increase in the expression of POD2 and POD7 genes, indicating a defense mechanism by root lignification. Conclusion Our results demonstrated that different metal biogenic nanoparticles cause different effects on soybean seedlings and these findings highlight the importance of investigating possible phytotoxic effects of these nanomaterials for the control of phytopathogens or as nanofertilizers.

Herein, a novel completely green biosensor was designed exploiting both the biological and instrumental components made of eco-friendly materials for the detection of herbicides encapsulated into biodegradable nanoparticles for a sustainable agriculture. Similar nanocarriers, indeed, can deliver herbicides to the correct location, reducing the amount of active chemicals deposited in the plant, impacting the agricultural and food industries less. However, handling measurements of nanoherbicides is crucial to provide comprehensive information about their status in the agricultural fields to support farmers in decision-making. In detail, whole cells of the unicellular green photosynthetic alga Chlamydomonas reinhardtii UV180 mutant were immobilized by a green protocol on carbonized lignin screen-printed electrodes and integrated into a photo-electrochemical transductor for the detection of nanoformulated atrazine. Specifically, atrazine encapsulated into zein and chitosan doped poly-ε-caprolactone nanoparticles (atrazine-zein and atrazine-PCL-Ch) were analyzed following the current signals at a fixed applied potential of 0.8 V, in a range between 0.1 and 5 µM, indicating a linear relationship in the measured dose-response curves and a detection limit of 0.9 and 1.1 nM, respectively. Interference studies resulted in no interference from 10 ppb bisphenol A, 1 ppb paraoxon, 100 ppb arsenic, 20 ppb copper, 5 ppb cadmium, and 10 ppb lead at safety limits. Finally, no matrix effect was observed on the biosensor response from wastewater samples and satisfactory recovery values of 106 ± 8% and 93 ± 7% were obtained for atrazine-zein and atrazine-PCL-Ch, respectively. A working stability of 10 h was achieved.

The encapsulation of atrazine into poly(epsilon-caprolactone) nanocapsules has been shown to improve the efficiency of the herbicide and decrease its environmental impacts. In the current work, we evaluated the efficiency of nanoatrazine in the post-emergence control of Alternanthera tenella Colla plants and performed a meta-analysis to compare the results with studies already published with other weeds. The first experiment was carried out in the field, where we observed that nanoatrazine (at 200 g a. i. ha−1) induced higher inhibition of the maximum quantum efficiency of photosystem II (up to 39%) than conventional atrazine at the same concentration. However, nanoencapsulation did not improve the visually-determined weed control by atrazine. To better understand the response of A. tenella plants to nanoatrazine, a second experiment was carried out in a greenhouse with four-leaf stage plants treated with nano and conventional atrazine at 200, 500, 1000, and 2000 g a. i. ha−1. Nanoatrazine showed higher efficiency (up to 33%) than commercial atrazine in inhibiting photosystem II activity at all doses until 48 h after application. Again, weed control and plant dry mass did not differ between formulations. From the meta-analysis, it was observed that A. tenella plants showed a response to nanoatrazine that differs from other target species, as the gain in efficiency resulting from the nanoencapsulation was restricted to the short-term analysis, and did not result in better weed control. These results reinforce that the efficiency of nanoatrazine is dependent on the studied species.

abstract: The objective of this study was to analyze the phytotoxic effects of poly (ɛ-caprolactone) (PCL) nanocapsules on mustard (Brassica juncea) seeds. The nanoformulations were prepared using two protocols: PCL nanocapsules containing Tween as a stabilizer (NC TW) and PCL nanocapsules containing poly(vinyl alcohol) (PVA), a polymer that has emulsifying properties (NC PVA). Two experimental systems were used (nanoformulations sprayed on the substrate and as seed treatment), each one in a factorial scheme with two formulations (NC TW and NC PVA) and five dilutions (0%, 25%, 50%, 75%, and 100% of the stock formulation). In general, intermediary concentrations of NC TW showed higher phytotoxicity than NC PVA, as indicated by sharper reductions in germination and increases in the percentage of abnormal seedlings. However, in the substrate treatment, NC PVA (100%) led to a sharper reduction in germination than NC TW in the same dilution. NC TW-treated seeds presented greater water absorption. In an additional assay with nanocapsules labeled with a fluorescent probe (rhodamine B), NC PVA-treated seeds showed higher fluorescence intensity in the seed coat. In the case of NC TW-treated seeds, the fluorescence signal tended to move to the seed interior as the nanocapsule levels increased. Moreover, the seed treatment with this formulation induced sharper increases in water uptake by the seeds than NC PVA. The different effects induced by NC TW and NC PVA could be related to the different characteristics of the nanocapsules, as the lower size and more negative charge of NC TW might have favored their entrance into the seeds.

Caryocar brasiliense Cambess is a plant species typical of the Cerrado, a Brazilian biome. The fruit of this species is popularly known as pequi, and its oil is used in traditional medicine. However, an important factor hindering the use of pequi oil is its low yield when extracted from the pulp of this fruit. Therefore, in this study, with aim of developing a new herbal medicine, we an-alyzed the toxicity and anti-inflammatory activity of an extract of pequi pulp residue (EPPR), fol-lowing the mechanical extraction of the oil from its pulp. For this purpose, EPPR was prepared and encapsulated in chitosan. The nanoparticles were analyzed, and the cytotoxicity of the encapsu-lated EPPR was evaluated in vitro. After confirming the cytotoxicity of the encapsulated EPPR, the following evaluations were performed with non-encapsulated EPPR: in vitro anti-inflammatory activity, quantification of cytokines, and acute toxicity in vivo. Once the anti-inflammatory activity and absence of toxicity of EPPR were verified, a gel formulation of EPPR was developed for topical use and analyzed for its in vivo anti-inflammatory potential, ocular toxicity, and previous stability assessment. EPPR and the gel containing EPPR showed effective anti-inflammatory activity and lack of toxicity. The formulation was stable. Thus, a new herbal medicine with anti-inflammatory activity can be developed from discarded pequi residue.

Abstract Background The advances in products based on nanotechnology have directed extensive research on low-cost, biologically compatible, and easily degradable materials. Main body Sericin (SER) is a protein mainly composed of glycine, serine, aspartic acid, and threonine amino acids removed from the silkworm cocoon (particularly Bombyx mori and other species). SER is a biocompatible material with economic viability, which can be easily functionalized due to its potential crosslink reactions. Also, SER has inherent biological properties, which makes possible its use as a component of pharmaceutical formulations with several biomedical applications, such as anti-tumor, antimicrobials, antioxidants and as scaffolds for tissue repair as well as participating in molecular mechanisms attributed to the regulation of transcription factors, reduction of inflammatory signaling molecules, stimulation of apoptosis, migration, and proliferation of mesenchymal cells. Conclusion In this review, the recent innovations on SER-based nano-medicines (nanoparticles, micelles, films, hydrogels, and their hybrid systems) and their contributions for non-conventional therapies are discussed considering different molecular mechanisms for promoting their therapeutic applications.

Abstract Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.

Digitaria insularis (sourgrass) is a monocotyledon weed of difficult control and high invasive behavior. Atrazine is widely applied in the Americas to control weeds in maize culture, but its efficiency against D. insularis is limited. The incorporation of atrazine into poly(epsilon-caprolactone) nanocapsules increased the herbicidal activity against susceptible weeds; however, the potential of this nanoformulation to control atrazine-tolerant weeds including D. insularis has not yet been tested. Here, we evaluated the post-emergent herbicidal activity of nanoatrazine against D. insularis plants during initial developmental stages. The study was carried out in a greenhouse, using pots filled with clay soil. Plants with two or four expanded leaves were treated with conventional or nanoencapsulated atrazine at 50 or 100% of the recommended dosage (1,000 or 2,000 g ∙ ha−1), followed by the evaluation of physiological, growth, and control parameters of the plants. Compared with conventional herbicide, both dosages of nanoatrazine induced greater and faster inhibition of D. insularis photosystem II activity at both developmental stages. Atrazine nanoencapsulation also improved the control of D. insularis plants, especially in the stage with two expanded leaves. In addition, nanoatrazine led to higher decreases of dry weight of fourleaved plants than atrazine. The use of the half-dosage of nanoatrazine was equally or more efficient in affecting most of the evaluated parameters than the conventional formulation at full dosage. Overall, these results suggest that the nanoencapsulation of atrazine potentiated its post-emergent herbicidal activity against D. insularis plants at initial developmental stages, favoring the control of this atrazine-tolerant weed.

The aim of this work was to synthesize polymeric microparticles as carriers for nitrogen, phosphorus, and potassium (NPK fertilizer) for agricultural applications, using polyglycerol (PG) to improve the synthesis procedure. Multivariate experimental designs were employed to obtain a satisfactory synthesis. The desirability function identified the best conditions for preparation of the microparticles as being 100.00 mg of poly(ε-caprolactone) (PCL), 825.00 mg of PG, 9.25 mL of chloroform, and 0.9% w/v of polyvinyl alcohol (PVA). This resulted in average encapsulation rates of 94.23% for N, 99.80% for P, and 65.00% for K. The profile of release from the microparticles was according to diffusion following Fick’s Law. These observations confirmed the capacity of the proposed microparticles to sustain a continuous and prolonged release of NPK for the purpose of plant fertilization. Keywords: Polymeric microparticles, Modified release, Fertilizers, Polyglycerol, Multivariate optimization

Nanoformulations have been used to improve the delivery of fertilizers, pesticides, and growth regulators, with a focus on more sustainable agriculture. Nanoherbicide research has focused on efficiency gains through targeted delivery and environmental risk reduction. However, research on the behavior and safety of the application of these formulations in cropping systems is still limited. Organic matter contained in cropping systems can change the dynamics of herbicide–soil interactions in the presence of nanoformulations. The aim of this study was to use classical protocols from regulatory studies to understand the retention and mobility dynamics of a metribuzin nanoformulation, compared to a conventional formulation. We used different soil systems and soil with added fresh organic material. The batch method was used for sorption–desorption studies and soil thin layer chromatography for mobility studies, both by radiometric techniques. Sorption parameters for both formulations showed that retention is a reversible process in all soil systems (H~1.0). In deep soil with added fresh organic material, nanoformulation was more sorbed (14.61 ± 1.41%) than commercial formulation (9.72 ± 1.81%) (p < 0.05). However, even with the presence of straw as a physical barrier, metribuzin in nano and conventional formulations was mobile in the soil, indicating that the straw can act as a barrier to reduce herbicide mobility but is not impeditive to herbicide availability in the soil. Our results suggest that environmental safety depends on organic material maintenance in the soil system. The availability can be essential for weed control, associated with nanoformulation efficiency, in relation to the conventional formulation.

Arboviral diseases are a threat to global public health systems, with recent data suggesting that around 40% of the world’s population is at risk of contracting arboviruses. The use of mosquito repellents is an appropriate strategy to avoid humans coming into contact with vectors transmitting these viruses. However, the cost associated with daily applications of repellents can make their use unfeasible for the low-income populations that most need protection. Therefore, the development of effective formulations offers a way to expand access to this means of individual protection. Consequently, research efforts have focused on formulations with smaller quantities of active agents and sustained release technology, aiming to reduce re-applications, toxicity, and cost. The present study investigates the development of nanostructured lipid carriers (NLCs) loaded with a mixture of the compounds icaridin (synthetic) and geraniol (natural), incorporated in cellulose hydrogel. The NLCs were prepared by the emulsion/solvent evaporation method and were submitted to physicochemical characterization as a function of time (at 0, 15, 30, and 60 days). The prepared system presented an average particle size of 252 ± 5 nm, with encapsulation efficiency of 99% for both of the active compounds. The stability profile revealed that the change of particle size was not significant (p > 0.05), indicating high stability of the system. Rheological characterization of the gels containing NLCs showed that all formulations presented pseudoplastic and thixotropic behavior, providing satisfactory spreadability and long shelf life. Morphological analysis using atomic force microscopy (AFM) revealed the presence of spherical nanoparticles (252 ± 5 nm) in the cellulose gel matrix. Permeation assays showed low fluxes of the active agents through a Strat-M® membrane, with low permeability coefficients, indicating that the repellents would be retained on the surface to which they are applied, rather than permeating the tissue. These findings open perspectives for the use of hybrid formulations consisting of gels containing nanoparticles that incorporate repellents effective against arthropod-borne virus. These systems could potentially provide improvements considering the issues of effectiveness, toxicity, and safety.

Abstract Pesticides and fertilizers are widely used to enhance agriculture yields, although the fraction of the pesticides applied in the field that reaches the targets is less than 0.1%. Such indiscriminate use of chemical pesticides is disadvantageous due to the cost implications and increasing human health and environmental concerns. In recent years, the utilization of nanotechnology to create novel formulations has shown great potential for diminishing the indiscriminate use of pesticides and providing environmentally safer alternatives. Smart nano-based pesticides are designed to efficiently delivery sufficient amounts of active ingredients in response to biotic and/or abiotic stressors that act as triggers, employing targeted and controlled release mechanisms. This review discusses the current status of stimuli-responsive release systems with potential to be used in agriculture, highlighting the challenges and drawbacks that need to be overcome in order to accelerate the global commercialization of smart nanopesticides.

To determine whether the permeation capacity and analgesic efficacy of articaine (ATC) could be increased and cytotoxicity decreased by encapsulation in poly(ɛ-caprolactone) nanocapsules (ATCnano), aiming at local or topical anesthesia in dentistry. Cellular viability was evaluated (using the MTT test and fluorescence microscopy) after 1 h and 24 h exposure of HaCaT cells to ATC, ATCnano, ATC with epinephrine (ATCepi), and ATC in nanocapsules with epinephrine (ATCnanoepi). The profiles of permeation of 2% ATC and 2% ATCnano across swine esophageal epithelium were determined using Franz-type vertical diffusion cells. Analgesic efficacy was evaluated with a von Frey anesthesiometer in a postoperative pain model in rats, comparing the 2% ATC, 2% ATCnano, 2% ATCepi, and 2% ATCnanoepi formulations to 4% ATCepi (a commercially available formulation). We show that use of the nanocapsules decreased the toxicity of articaine (P

Trichoderma harzianum is a biological control agent used against phytopathogens and biostimulation in agriculture. However, its efficacy can be affected by biotic and abiotic factors, and microencapsulation has been used to maximize the efficacy. The objective was to develop polymeric microparticles to encapsulate T. harzianum, to perform physicochemical characterization to evaluate its stability, to evaluate effects on the soil microbiota, antifungal activity in vitro and enzymatic activity. Size distribution of wet and dry microparticles was 2000 and 800 μm, respectively. Scanning electron microscopy showed spherical morphology and encapsulation of T. harzianum. Photostability assays showed that encapsulation protected the fungus against ultraviolet radiation. The evaluation of the microbiota showed that the proportion of denitrifying bacteria increased when compared to the control. The T. harzianum encapsulation showed an improvement in the chitinolytic and cellulosic activity. In vitro tests showed that encapsulated fungus were able to provide a greater control of S. sclerotiorum.

Arboviruses such as yellow fever, dengue, chikungunya and zika are transmitted mainly by the mosquito vector Aedes aegypti. Especially in the tropics, inefficacy of mosquito control causes arboviruses outbreaks every year, affecting the general population with debilitating effects in infected individuals. Several strategies have been tried to control the proliferation of A. aegypti using physical, biological, and chemical control measures. Other methods are currently under research and development, amongst which the use of nanotechnology has attracted a lot of attention of the researchers in relation to the production of more effective repellents and larvicides with less toxicity, and development of rapid sensors for the detection of virus infections. In this review, the utilization of nano-based formulations on control and diagnosis of mosquito-borne diseases were discussed. We also emphasizes the need for future research for broad commercialization of nano-based formulations in world market aiming a positive impact on public health.

Mucoadhesive polymeric nanocapsules have attracted interest of researchers from different fields from natural sciences because of their ability to interact with the mucosa and increase drug permeation. Anesthesia by immersion causes absorption through the skin and gills of fish, so it is important to evaluate the exposure of these organs to drug nanosystems. Benzocaine (BENZ) is one of the most popular anesthetic agents used in fish anesthesia, but it has drawbacks because of its low bioavailability, resulting in weak absorption after immersion. Here we describe method developed for preparing and characterizing chitosan-coated PLGA mucoadhesive nanoparticles containing BENZ (NPMAs) for zebrafish immersion anesthesia. We determined the lowest effective concentration, characterized the interaction of the mucoadhesive system with fish, measured the anesthetic efficacy, and evaluated possible toxic effects in embryos and adults exposed to the nanoformulations. This study opens perspectives for using nanoformulations prepared with BENZ in aquaculture, allowing reduction of dosage as well as promoting more effective anesthesia and improved interaction with the mucoadhesive system of fish.

Abstract Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner. Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc.) in the treatment of various diseases. The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker molecules. The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed. In addition, we have included information regarding the trends and perspectives in nanomedicine area.

Organogels (ORGs) are semi-solid materials, in which an organic phase is immobilized by a three-dimensional network composed of self-organized system, forming the aqueous phase. In this context, lipid–Pluronics (PLs) ORGs form a two-phase system which can be effectively used as skin delivery systems, favoring their permeation across the skin. In this study, we presented the development of ORG skin drug-delivery systems for curcumin (CUR), a liposoluble phenolic pigment extracted from the turmeric rhizome. In special, we designed the formulation compositions in order to carry high amounts of CUR soluble in oleic acid (OA), as organic phase, entrapped into an aqueous phase composed of micellar PL-based hydrogels by associating two polymers with different hydrophilic–lipophilic balances, Pluronic F-127 (PL F-127), and Pluronic L-81 (PL L-81), to enhance the permeation across the skin. Results revealed that the incorporation of PL L-81 favored the CUR incorporation into micelle–micelle interface. CUR insertion into OA-PL F-127/L-81 reduced both G’/G” relationship (∼16 x) and viscosity values (η* ∼ 54 mPa.s, at 32.5°C), disturbing the ORG network structural organization. In vitro permeation assays through Strat-M® skin-model membranes showed that higher CUR-permeated amounts were obtained for OA-PL F-127/L-81 (4.83 µg.cm−2) compared to OA-PL F-127 (3.51 μg.cm−2) and OA (2.25 μg.cm−2) or hydrogels (∼1.2 μg.cm−2, p < 0.001). Additionally, ORG formulations presented low cytotoxic effects and evoked pronounced antileishmanial activity (IC50 < 1.25 µg.ml−1), suggesting their potential use as skin delivery systems against Leishmania amazonensis. Results from this study pointed out OA-PL-based ORGs as promising new formulations for possible CUR topical administration.

Our agriculture is threatened by climate change and the depletion of resources and biodiversity. A new agriculture revolution is needed in order to increase the production of crops and ensure the quality and safety of food, in a sustainable way. Nanotechnology can contribute to the sustainability of agriculture. Seed nano-priming is an efficient process that can change seed metabolism and signaling pathways, affecting not only germination and seedling establishment but also the entire plant lifecycle. Studies have shown various benefits of using seed nano-priming, such as improved plant growth and development, increased productivity, and a better nutritional quality of food. Nano-priming modulates biochemical pathways and the balance between reactive oxygen species and plant growth hormones, resulting in the promotion of stress and diseases resistance outcoming in the reduction of pesticides and fertilizers. The present review provides an overview of advances in the field, showing the challenges and possibilities concerning the use of nanotechnology in seed nano-priming, as a contribution to sustainable agricultural practices.

Chrysophanol is a unique anthraquinone having broad-spectrum therapeutic potential along with ecological importance. It is the first polyketide that has been reported to be biosynthesized in an organism-specific manner. The traditional Chinese and Korean medicinal systems provide evidence of the beneficial effects of chrysophanol on human health. The global distribution of chrysophanol encountered in two domains of life (bacteria and eukaryota) has motivated researchers to critically evaluate the properties of this compound. A plethora of literature is available on the pharmacological properties of chrysophanol, which include anticancer, hepatoprotective, neuroprotective, anti-inflammatory, antiulcer, and antimicrobial activities. However, the pharmacokinetics and toxicity studies on chrysophanol demand further investigations for it to be used as a drug. This is the first comprehensive review on the natural sources, biosynthetic pathways, and pharmacology of chrysophanol. Here we reviewed recent advancements made on the pharmacokinetics of the chrysophanol. Additionally, we have highlighted the knowledge gaps of its mechanism of action against diseases and toxicity aspects.

In current agricultural practices, the control of pests is often accomplished by means of the excessive use of agrochemicals, which can result in environmental pollution and the development of resistant pests. A major challenge of agriculture is to increase food production to meet the needs of the growing world population, without damaging the environment. In this context, biopesticides can offer a better alternative to synthetic pesticides, enabling safer control of pest populations. However, limitations of biopesticides, including short shelf life, photosensitivity, and volatilization, make it difficult to use them on a large scale. Here, we investigate the potential use of neem oil in crop protection, considering the gaps and obstacles associated with the development of sustainable agriculture in the not too distant future.

Recent scientific data indicate that nanotechnology has the potential to positively impact the agrifood sector, minimizing adverse problems of agricultural practices on environment and human health, improving food security and productivity (as required by the predicted rise in global population), while promoting social and economic equity. In this context, we select and report on recent trends in nanomaterial-based systems and nanodevices that could provide benefits on the food supply chain specifically on sustainable intensification, and management of soil and waste. Among others, nanomaterials for controlled-release of nutrients, pesticides and fertilizers in crops are described as well as nanosensors for agricultural practices, food quality and safety.

15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has physiological properties including pronounced anti-inflammatory activity, though it binds strongly to serum albumin. The use of solid lipid nanoparticles (SLN) can improve therapeutic properties increasing drug efficiency and availability. 15d-PGJ2-SLN was therefore developed and investigated in terms of its immunomodulatory potential. 15d-PGJ2-SLN and unloaded SLN were physicochemically characterized and experiments in vivo were performed. Animals were pretreated with 15d-PGJ2-SLN at concentrations of 3, 10 or 30 μg·kg-1 before inflammatory stimulus with carrageenan (Cg), lipopolysaccharide (LPS) or mBSA (immune response). Interleukins (IL-1β, IL-10 and IL-17) levels were also evaluated in exudates. The 15d-PGJ2-SLN system showed good colloidal parameters and encapsulation efficiency of 96%. The results showed that the formulation was stable for up to 120 days with low hemolytic effects. The 15d-PGJ2-SLN formulation was able to reduce neutrophil migration in three inflammation models tested using low concentrations of 15d-PGJ2. Additionally, 15d-PGJ2-SLN increased IL-10 levels and reduced IL-1β as well as IL-17 in peritoneal fluid. The new 15d-PGJ2-SLN formulation highlights perspectives of a potent anti-inflammatory system using low concentrations of 15d-PGJ2.

In this study, polymeric nanocapsules of PCL containing the herbicide atrazine were prepared. In order to optimize the preparation conditions, a 2³ factorial design was performed using different formulations of nanocapsules, which investigated the influence of three variables at two levels. The factors varied were the quantities of PCL, Span 60 and Myritol. The results were evaluated considering the size, polydispersity, zeta potential and association rate and the measures of these parameters were taken immediately after preparation and after 30 days of preparation. The formulations with minimum level of polymer in the preparation showed better stability results.

Agrochemicals constitute the class of products most commonly found in water resources. Their high level of concentration is due to the fact that less than 0.1% of pesticides applied to crops reach their target. The present work aims to study the sorption of clomazone herbicide (associated or not with nanoparticles). The sorption tests, performed with the 2(4) factorial design, showed that the form of herbicide is the main factor for sorption of clomazone. The application of nanoparticles as delivery system for agrochemicals is a pressing area of study and can contribute for decrease in effects of clomazone in the environment.

The knowledge of the structure characteristic of the Organic Matter is important for the understanding of the natural process. In this context aquatic humic substances (principal fraction) were isolated from water sample collected from the two distinct rivers, using procedure recommended for International Humic Substances Society and characterized by elemental analysis, electron paramagnetic resonance and nuclear magnetic resonance (13C NMR). The results were interpreted using principal component analysis (PCA) and the statistical analyses showed different in the structural characteristics of the aquatic humic substances studied.

In this paper we describe the preparation poly (L-lactide) (PLA) nanocapsules as a drug delivery system for the local anesthetic benzocaine. The characterization and in vitro release properties of the system were investigated. The characterization results showed a polydispersity index of 0.14, an average diameter of 190.1± 3 nm, zeta potential of -38.5 mV and an entrapment efficiency of 73%. The release profile of Benzocaine loaded in PLA nanocapsules showed a significant different behavior than that of the pure anesthetic in solution. This study is important to characterize a drug release system using benzocaine for application in pain treatment.

Cellulose acetate polymeric membranes had been prepared by a procedure of two steps, combining the method of phase inversion and the technique of hydrolysis-deposition. The first step was the preparation of the membrane, and together was organomodified with tetraethylortosilicate and 3-aminopropyltrietoxysilane. Parameters that exert influence in the complexation of the metallic ion, as pH, time of complexation, metal concentration, had been studied in laboratory using tests of metal removal. The membranes had presented resistance mechanics and reactivity to cations, being able to be an alternative for the removal, daily pay-concentration or in the study of the lability of metals complexed.

In this paper, we describe the preparation of alginate nanoparticles as a delivery system for the herbicide clomazone. Two different methods were investigated and characterized by size distribution, zeta potencial, pH and in vitro release. The alginate/AOT nanoparticles had higher rates of association of the herbicide clomazone than alginate/chitosan nanoparticles. Clomazone release profile, showed a significant difference in release behavior of pure herbicide in solution when compared with herbicide loaded in both alginate nanoparticles. This study is important to construct a biodegradable release system using herbicide for later release into more specific targets, avoiding contamination of environmental matrices.

Hydroxymethylnitrofurazone (NFOH) is a prodrug that is active against Trypanosoma cruzi. It however presents low solubility and high toxicity. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) can be used as a drug-delivery system for NFOH modifying its physico-chemical properties. The aim of this work is to characterize the inclusion complex between NFOH and HP-beta-CD. The rate of NFOH release decreases after complexation and thermodynamic parameters from the solubility isotherm studies revealed that a stable complex is formed (deltaGº= 1.7 kJ/mol). This study focuses on the physico-chemical characterization of a drug-delivery formulation that comes out as a potentially new therapeutic option for Chagas disease treatment.

Bupivacaine (S75-R25, NovaBupi®) is an amide type local anesthetic widely used. The present work consists of the development and validation of analytical methodology for evaluation of NovaBupi® content in the poly-lactide-co-glycolide nanospheres (PLGA-NS) by high performance liquid chromatography. The separation was made using the reversed-phase column LC-18, acetonitrile/phosphate buffer 85:15 v/v as mobile phase and detection at 220 nm. The results obtained show that the analytical methodology is accurate, reproducible, robust and linear over the concentration range 10-220.0 g/mL of NovaBupi®. The method was applied to determine the encapsulation efficiency and evaluate the release profile of NovaBupi®, showing good results.

Many theories about the mechanism of action of local anesthetics (LA) are described in the literature. Two types of theories can be distinguished: those that focus on the direct effects of LA on their target protein in the axon membranes, i.e. the voltage-gated sodium channel and the ones that take into account the interaction of anesthetic molecules with the lipid membrane phase for the reversible nerve blockage. Since there is a direct correlation between LA hydrophobicity and potency, it is crucial to take this physico-chemical property into account to understand the mechanism of action of LA, be it on the sodium channel protein, lipid(s), or on the whole membrane phase.

Characteriza of the inclusion complex ropivacaine: beta-cyclodextrin. Ropivacaine (RVC) is a widely used local anesthetic. The complexation of RVC with beta-cyclodextrin (beta-CD) is of great interest for the development of more efficient local anesthetic formulations. The present work focuses on the characterization of the RVC:beta-CD complex by nuclear magnetic resonance (NMR). The stoichiometry of the complex is 1:2 RVC:beta-CD. DOSY-NMR shows that the association constant is 55.5 M-1. Longitudinal relaxation time results show that RVC changes its mobility in the presence of beta-CD. This study is focused on the physicochemical characterization of inclusion complexes that are potentials options for pain treatment.

S(-) Bupivacaine (S(-)BVC) and Lidocaine (LDC) are widely used local anesthetics (LA). Hydroxypropyl beta-cyclodextrin (HP-beta-CD) is used as a drug-carrier system. The aim of this work was to characterize inclusion complexes between LA and HP-beta-CD. The affinity constants determined at different pHs show favourable complexation. The release kinetics experiments showed that S(-)BVC and LDC changed the released profiles in the presence of HP-beta-CD. Nuclear magnetic resonance experiments gave information about the interaction between LA and the cyclodextrin cavity. This study focused on the physicochemical characterization of drug-delivery formulations that come out as potentially new therapeutic options for pain treatment.

Poly(epsilon-caprolactone) (PCL) nanocapsules have been used as a carrier system for the herbicide atrazine, which is commonly applied to maize. We demonstrated previously that these atrazine containing polymeric nanocapsules were ten-fold more effective in the control of mustard plants (a target species), as compared to a commercial atrazine formulation. Since atrazine can have adverse effects on non-target crops, here we analyzed the effect of encapsulated atrazine on growth, physiological and oxidative stress parameters of soil-grown maize plants (Zea mays L.). One day after the post-emergence treatment with PCL nanocapsules containing atrazine (1 mg mL-1), maize plants presented 15 and 21 % decreases in maximum quantum yield of photosystem II and in net CO2 assimilation rate, respectively, as compared to water-sprayed plants. The same treatment led to a 1.8-fold increase in leaf lipid peroxidation in comparison with control plants. However, all of these parameters were unaffected four and eight days after the application of encapsulated atrazine. These results suggested that the negative effects of atrazine were transient, probably due to the ability of maize plants to detoxify the herbicide. When encapsulated atrazine was applied at a ten-fold lower concentration (0.1 mg mL-1), a dosage that is still effective for weed control, no effects were detected even shortly after application. Regardless of the herbicide concentration, neither pre- nor post-emergence treatment with the PCL nanocapsules carrying atrazine resulted in the development of any macroscopic symptoms in maize leaves, and there were no impacts on shoot growth. Additionally, no effects were observed when plants were sprayed with PCL nanocapsules without atrazine. Overall, these results suggested that the use of PCL nanocapsules containing atrazine did not lead to persistent side effects in maize plants, and that the technique could offer a safe tool for weed control without affecting crop growth.

Poly(epsilon-caprolactone) (PCL) nanocapsules have been recently developed as a modified release system for atrazine, an herbicide that can have harmful effects in the environment. Here, the post-emergence herbicidal activity of PCL nanocapsules containing atrazine was evaluated using mustard (Brassica juncea) as target plant species model. Characterization of atrazine-loaded PCL nanocapsules by nanoparticle tracking analysis indicated a concentration of 7.5 x 10(12) particles mL(-1) and an average size distribution of 240.7 nm. The treatment of mustard plants with nanocapsules carrying atrazine at 1 mg mL(-1) resulted in a decrease of net photosynthesis and PSII maximum quantum yield, and an increase of leaf lipid peroxidation, leading to shoot growth inhibition and the development of severe symptoms. Time course analysis until 72 h after treatments showed that nanoencapsulation of atrazine enhanced the herbicidal activity in comparison with a commercial atrazine formulation. In contrast to the commercial formulation, ten-fold dilution of the atrazine-containing nanocapsules did not compromise the herbicidal activity. No effects were observed when plants were treated with nanocapsules without herbicide compared to control leaves sprayed with water. Overall, these results demonstrated that atrazine-containing PCL nanocapsules provide very effective post-emergence herbicidal activity. More importantly, the use of nanoencapsulated atrazine enables the application of lower dosages of the herbicide, without any loss of efficiency, which could provide environmental benefits.

Polarizability correlates well with organic ion stabilization in solution and can be defined as a measure of the relative ease of the distortion of the electronic cloud of a dipolar system exposed to an external electric field. The effective atomic polarizability, alphad, has a fundamental influence on chemical reactivity in the gas phase and in solution. In terms of chemical reactivity the charge is generated within the molecule as a positive charge due to protonation, ionization or resulting from the attack of a nucleophilic anion. In this paper, lipoidal diaminedithiol (DADT) perfusion radioligands based on 99Tc m and possessing an alkylamine side chain have been used to check the influence of alphad on their brain uptake. Some new DADT derivatives, respectively DADT-DIPA (diaminedithiol - diisopropylamine), DADT DIBA (diaminedithiol diisobutylamine), DADT-PR (diaminedithiol - branched pyperidine), have been designed to have high nitrogen alkylamine alphad values. In spite of the fact of higher alphad values having been correlated to higher brain uptakes, there isn't a clear mechanism able to trap these radioligands into the brain space.

JUSTIFICATIVA E OBJETIVOS: Com a finalidade de prolongar a duração de ação e reduzir a toxicidade sistêmica, têm-se desenvolvido formulações de anestésicos locais (AL) complexados com ciclodextrinas (CD). Este estudo realizou a caracterização físico-química e avaliou, em ratos, os efeitos dos complexos de inclusão de bupivacaína racêmica (S50-R50) e da mistura com excesso enantiomérico de 50% (S75-R25) de bupivacaína com hidroxipropil-betaciclodextrina (HP-beta-CD), comparando-os com as soluções atualmente utilizadas na clínica. MÉTODO: Os complexos de inclusão de S75-R25 em HP-beta-CD (razão molar 1:1) foram caracterizados por estudos de solubilidade de fases variando-se as concentrações de HP-beta-CD e a temperatura. Determinaram-se as constantes de afinidade (K) pela HP-beta-CD e os parâmetros termodinâmicos para a complexação. Os bloqueios motor e sensitivo foram avaliados, por meio da administração subaracnóidea das formulações na concentração clínica de 0,5%. RESULTADOS: A formação de complexos de inclusão foi observada pelo aumento da solubilidade aquosa do AL sob diferentes temperaturas e concentrações de HP-beta-CD. Os testes in vivo mostraram que S50-R50HP-beta-CD e S75-R25HP-beta-CD reduziram a latência (p < 0,001) sem alterar o tempo de recuperação do bloqueio motor, tempo para efeito máximo e efeito total dos fármacos. Além disso, ambas as formulações aumentaram a intensidade (1,5 vez, p < 0,001) e prolongaram a duração da analgesia, com relação aos fármacos livres. CONCLUSÕES: Os complexos S50-R50HP-beta-CD e S75-R25HP-beta-CD potencializaram o bloqueio nervoso diferencial, podendo ser utilizados para reduzir a freqüência de administrações ou a dose de AL para indução de um mesmo efeito. A formulação contendo a mistura com excesso enantiomérico de 50% (S75-R25) de bupivacaína mostrou-se interessante no desenvolvimento de formulações seguras e úteis para o tratamento da dor aguda no período pós-operatório.JUSTIFICATIVA Y OBJETIVOS: Con la finalidad de prolongar la duración de la acción y reducir la toxicidad sistémica, se han desarrollado formulaciones de AL con complejo de ciclodextrinas (CD). Ese estudio realizó la caracterización físico-química y evaluó en ratones, los efectos de los complejos de inclusión de bupivacaína racémica (S50-R50) y de la mezcla con exceso enantiomérico de 50% (S75-R25) de bupivacaína con hidroxipropil-betaciclodextrina (HP-beta-CD), comparándolos con las soluciones actualmente utilizadas en la clínica. MÉTODO: Los complejos de inclusión de S75-R25 en HP-beta-CD (razón molar 1:1) fueron caracterizados por estudios de solubilidad de fases variando las concentraciones de HP-beta-CD y la temperatura. Fueron determinadas las constantes de afinidad (K) por la HP-beta-CD y los parámetros termodinámicos para los complejos. Los bloqueos motor y sensitivo fueron evaluados en ratones, a través de la administración subaracnoidea de las formulaciones en la concentración clínica de 0,5%. RESULTADOS: La formación de complejos de inclusión se observó a través del aumento de la solubilidad acuosa del AL bajo diferentes temperaturas y concentraciones de HP-beta-CD. Las pruebas in vivo mostraron que S50-R50HP-beta-CD y S75-R25HP-beta-CD redujeron la latencia (p < 0,001) sin alterar el tiempo de recuperación del bloqueo motor, tiempo para efecto máximo y efecto total de los fármacos. Además, ambas formulaciones aumentaron la intensidad (1,5 veces, p < 0,001) y prolongaron la duración de la analgesia, con relación a los fármacos libres. CONCLUSIONES: Los complejos, S50-R50HP-beta-CD y S75-R25HP-beta-CD, potenciaron el bloqueo nervioso diferencial, pudiendo ser utilizados para reducir la frecuencia de administraciones o la dosis de AL para inducción de un mismo efecto. La formulación conteniendo la mezcla con exceso enantiomérico de 50% (S75-R25) de bupivacaina fue interesante en el desarrollo de formulaciones seguras y útiles para el tratamiento del dolor agudo en el período postoperatorio.BACKGROUND AND OBJECTIVES: In order to prolong the action and reduce systemic toxicity, formulations of local anesthetic (LA) complexed with cyclodextrins (CD) have been developed. This study determined the physical-chemical characterization and evaluated the effects of inclusion complexes of racemic bupivacaine (S50-R50) and 50% enantiomeric excess (S75-R25) bupivacaine with hydroxypropil-beta-cyclodextrin (HP-beta-CD) in rats, and comparing them with the solutions currently used in the clinical practice. METHODS: Inclusion complexation of S75-R25 with HP-beta-CD (equimolar ratio 1:1) was characterized by phase-solubility studies varying the concentrations of HP-beta-CD and the temperature. Affinity constants (K) for HP-beta-CD and the thermodynamic parameters for complexation were determined. Motor and sensitive anesthesias were evaluated through the subarachnoid administration of the formulations in the concentration of 0.5%. RESULTS: Inclusion complexation was observed through the increase in aqueous solubility of LA in different temperatures and concentrations of HP-beta-CD. The in vivo tests demonstrated that S50-R50HP-beta-CD and S75-R25HP-beta-CD reduced latency (p < 0.001) without changing the recovery time of the motor block, time for maximal effect, and total effect of the drugs. Besides, both formulations increased the intensity (1.5 times, p < 0.001) and prolonged the duration of analgesia compared to the free drugs. CONCLUSIONS: The complexes S50-R50HP-beta-CD and S75-R25HP-beta-CD potentiated the differential nervous block, and can be used to reduce the frequency of administration or the dose of the LA to induce the same effect. The formulation containing enantiomeric excess (S75-R25) bupivacaine showed to be interesting in the development of safer formulations, and useful for the treatment of acute pain in the postoperative period.

JUSTIFICATIVA E OBJETIVOS: Os efeitos adversos associados ao uso de bupivacaína levaram à procura por novos anestésicos locais (AL) com perfil de bloqueio semelhante e menos tóxicos, surgindo novas preparações como a mistura enantiomérica de bupivacaína (S75-R25). Os sistemas de liberação controlada, contendo AL em carreadores como ciclodextrinas (CD), têm como objetivo melhorar a eficácia anestésica e o índice terapêutico dessas drogas. Este estudo visou a preparação, a caracterização e a avaliação da eficácia anestésica dos complexos de inclusão da mistura enantiomérica da bupivacaína (S75-R25) e da bupivacaína racêmica (S50-R50) com hidroxipropilb-ciclodextrina (HPb-CD) comparando-os com as preparações atualmente utilizadas na clínica. MÉTODO: Os complexos de inclusão foram preparados misturando-se quantidades apropriadas de HPb-CD e S50-R50 ou S75-R25 nas razões molares (1:1 e 1:2) e caracterizados por estudos de solubilidade de fases. Determinaram-se as constantes de afinidade (K) de cada AL pela HPb-CD. Os bloqueios motor e sensorial induzidos pelas drogas livres e complexadas foram avaliados, em camundongos, através do bloqueio do nervo ciático. Para a realização dos experimentos, utilizaram-se três concentrações de AL: 0,125%; 0,25% e 0,5%. RESULTADOS: Os estudos de solubilidade indicaram a formação de complexos de inclusão de S50-R50 e S75-R25 com HPb-CD, com valores de constante de afinidade (K) similares para os dois anestésicos: 14,7 M-1 (S50-R50:HP-bCD) e 14,3 M-1 (S75-R25:HP-bCD). Os testes em animais mostraram que a complexação potencializou o bloqueio nervoso diferencial induzido pelos AL: i) a duração do bloqueio motor induzido por S75-R25 foi similar à do S50-R50, mas menos intenso (p < 0,001). Já os complexos, S50-R50HPb-CD e S75-R25HPb-CD reduziram a latência (p < 0,01 e p < 0,05, respectivamente) sem modificar a intensidade do bloqueio motor (Emáx), em relação às drogas livres; ii) a avaliação do bloqueio sensorial mostrou aumento na intensidade da analgesia com os sistemas S50-R50HPb-CD (2 vezes, p < 0,001) e S75-R25HPb-CD (1,5-1,8 vezes; p < 0,01 e p < 0,001, respectivamente), nas duas proporções molares (1:1 e 1:2, AL:CD), além do prolongamento da duração do efeito analgésico, quando comparados às formulações S50-R50 e S75-R25. CONCLUSÕES: Os efeitos analgésicos mais pronunciados, obtidos após a complexação com HPb-CD, mostram que ambas as formulações, S50-R50HPb-CD e S75-R25HPb-CD, são de grande interesse para o alívio da dor no período pós-operatório, com a vantagem de serem administradas em menores concentrações. Entretanto, há que se ressaltar que a mistura enantiomérica de bupivacaína (S75-R25), por ser menos tóxica, representa uma alternativa no desenvolvimento de formulações de liberação controlada mais seguras e eficazes do que com a bupivacaína racêmica (S50-R50).JUSTIFICATIVA Y OBJETIVOS: Los efectos adversos asociados al uso de bupivacaína llevaron a la búsqueda por nuevos anestésicos locales (AL) con perfil de bloqueo semejante y menos tóxicos, surgiendo nuevas preparaciones como la mezcla enantiomérica de bupivacaína (S75-R25). Los sistemas de liberación controlada, conteniendo AL en carreadores como ciclodextrinas (CD), tienen como objetivo mejorar la eficacia anestésica y el índice terapéutico de esas drogas. Este estudio visó la preparación, caracterización y evaluación de la eficacia anestésica de los complejos de inclusión de la mezcla enantiomérica de la bupivacaína (S75-R25) y de la bupivacaína racémica (S50-R50) con hidroxipropilb-ciclodextrina (HPb-CD) comparándolos con las preparaciones actualmente utilizadas en la clínica. MÉTODO: Los complejos de inclusión fueron preparados mezclándose cantidades apropiadas de HPb-CD y S50-R50 ó S75-R25 en las razones molares (1:1 y 1:2) y caracterizados por estudios de solubilidad de fases. Se determinaron las constantes de afinidad (K) de cada AL por la HPb-CD. Los bloqueos motor y sensorial inducidos por las drogas libres y complejadas fueron evaluados en ratones, a través del bloqueo del nervio ciático. Para la realización de los experimentos, se utilizaron tres concentraciones de AL: 0,125; 0,25 y 0,5%. RESULTADOS: Los estudios de solubilidad indicaron la formación de complejos de inclusión de S50-R50 y S75-R25 con HPb-CD, con valores de constante de afinidad (K) análogos para los dos anestésicos: 14,7 M-1 (S50-R50: HP-bCD) y 14,3 M-1 (S75-R25: HP-bCD). Las pruebas en animales mostraron que la complejidad potenció el bloqueo nervioso diferencial inducido por los AL: i) la duración del bloqueo motor inducido por S75-R25 fue análogo al del S50-R50, pero menos intenso (p < 0,001). Ya los complejos, S50-R50HPb-CD y S75-R25 HPb-CD redujeron la latencia (p < 0,01 y p < 0,05, respectivamente) sin modificar la intensidad del bloqueo motor (Emáx), con relación a las drogas libres; ii) la evaluación del bloqueo sensorial mostró un aumento en la intensidad de la analgesia con los sistemas S50-R50 HPb-CD (2 veces, p < 0,001) y S75-R25 HPb-CD (1,5-1,8 veces; p < 0,01 y p < 0,001, respectivamente), en las dos proporciones molares (1:1 y 1:2, AL:CD), además del prolongamiento de la duración del efecto analgésico, cuando comparados a las formulaciones S50-R50 y S75-R25. CONCLUSIONES: Los efectos analgésicos más pronunciados logrados después de la complexación con HPb-CD muestran que ambas formulaciones, S50-R50 HPb-CD y S75-R25 HPb-CD, son de grande interés para el alivio del dolor en el período postoperatorio, con la ventaja de ser administradas en menores concentraciones. Mientras, hay que resaltar que la mezcla enantiomérica de bupivacaína (S75-R25), por ser una droga menos tóxica, representa una alternativa en el desarrollo de formulaciones de liberación controlada más seguras y eficaces de que con la bupivacaína racémica (S50-R50).BACKGROUND AND OBJECTIVES: Bupivacaine-induced side effects have led to the search for new local anesthetics (LA) with similar potency and lower toxicity, such as bupivacaine enantiomeric mixture (S75-R25). Drug-delivery systems for LA in carriers, such as cyclodextrins (CD), have been developed to improve anesthetic potency and therapeutic index of those drugs. This study aimed at preparing, characterizing and evaluating the anesthetic efficacy of inclusion complexes of bupivacaine enantiomeric mixture (S75-R25) and racemic bupivacaine (S50-R50) with hydroxypropylb- cyclodextrin (HPb-CD) comparing them to clinically available preparations. METHODS: Inclusion complexes were obtained by mixing appropriate volumes of HPb-CD and S50-R50 or S75-R25 to final 1:1 or 1:2 molar ratios and were characterized by phase solubility experiments. Affinity constants (K) were determined between HPb-CD and each LA. Motor and sensory blocks induced by plain or complexed LA formulations were evaluated in mice by sciatic nerve block. Three LA concentrations were used during the experiment: 0.125, 0.25 and 0.5%. RESULTS: Solubility experiments results were indicative of S50-R50:HPb-CD and S75-R25:HPb-CD complexation, with similar affinity constant (K) values: 14.7 M-1 and 14,3 M-1, respectively. In vivo experiments have shown that complexation has enhanced differential nerve blockade induced by LA: i) motor blockade duration induced by S75-R25 was similar, to the induced by but less intense S50-R50 ( p < 0.001). S50-R50HPb-CD and S75-R25HPb-CD complexes have decreased onset (p < 0.01 and p < 0.05, respectively), without changing motor block intensity (Emax) as compared to plain drugs; ii) sensory block evaluation has revealed higher analgesic intensity with S50-R50HPb-CD (2-fold, p < 0.001) and S75-R25HPb-CD (1.5-1.8-fold, p < 0.01 and p < 0.001, respectively) with both molar ratios (1:1 and 1:2, LA:CD), in addition to prolonging analgesic effect as compared to S50-R50 and S75-R25. CONCLUSIONS: More pronounced analgesic effects obtained by complexation with HPb-CD have shown that both formulations, S50-R50HPb-CD and S75-R25HPb-CD, are very useful for postoperative pain relief, requiring lower LA concentrations. Nevertheless, it is worth noticing that S75-R25 - being less toxic than racemic bupivacaine - is an interesting alternative for the development of more effective and safe drug-delivery systems as compared to racemic bupivacaine (S50-R50).

The study of characteristics of nanoscale structures and applications now has great interest of researchers from different areas. In this regard, lipid carriers can improve the bioavailability of drugs and the reduction of possible toxicological effects. Thus, the development of nanostructured systems for the agricultural sector, aimed at combating parasites may reduce extensive damage caused to livestock producers and animal health. This study aimed to prepare and characterize lipid carrier systems, such as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC), as well as evaluate the potential of cyto and genotoxicity of these systems in order to improve and produce alternatives to the use targeting these compounds in veterinary applications. Lipid nanoparticles had become spherical with an average size of 250 nm and remained stable over 120 days. The encapsulation efficiency was greater than 99% for both drugs and release tests showed a strong interaction between drugs and nanoparticles. Cyto- and genotoxicity tests show that nanoparticles made possible changes in cellular viability of the tested cells. Thus, the results showed that the nanoparticles had good colloidal characteristics without changes in its characteristics, enabling the development of carrier systems for these drugs , aiming veterinary applications.

This study presents the toxicological effects of iron nanoparticles (NP Fe2O3) using in vitro and in vivo tests. Initially nanoparticles were characterized physic-chemically followed by evaluation of cell viability using different cell lines. Allium cepa test and comet assay (cell lines and Danio rerio) were used for evaluation of genotoxicity. Oxidative stress analyses were performed using D. rerio exposed to NP-Fe2O3, and the enzymatic activity of the enzymes catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were evaluated. The results showed that initially nanoparticles had 65.55 nm, 0.24 of polydispersity of and 11.4 mV of zeta potential. Regarding cell viability, it was observed that this did not reach the IC50 up to the concentration 1 x 1010 NP mL-1. The in vitro comet assay showed that in concentrations 1.96 x108 and 109 NPs mL-1 these presented toxicity, for Allium cepa evaluation in concentrations 19.6 and 39.0 x109 NPs mL-1 presented significant damages when compared to the control. Oxidative stress showed that the liver was the most affected organ when compared to the control. Although studies show that iron nanoparticles do not lead to changes, further studies are needed to make sure they do not lead to environmental changes.

This study reports an investigation of the pharmacological activity, cytotoxicity and local effects of a liposomal formulation of the novel local anaesthetic ropivacaine (RVC) compared with its plain solution. RVC was encapsulated into large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine, cholesterol and α-tocopherol (4:3:0.07, mole %). Particle size, partition coefficient determination and in-vitro release studies were used to characterize the encapsulation process. Cytotoxicity was evaluated by the tetrazolium reduction test using sciatic nerve Schwann cells in culture. Local anaesthetic activity was assessed by mouse sciatic and rat infraorbital nerve blockades. Histological analysis was performed to verify the myotoxic effects evoked by RVC formulations. Plain (RVCPLAIN) and liposomal RVC (RVCLUV) samples were tested at 0.125%, 0.25% and 0.5% concentrations. Vesicle size distribution showed liposomal populations of 370 and 130 nm (85 and 15%, respectively), without changes after RVC encapsulation. The partition coefficient value was 132 ± 26 and in-vitro release assays revealed a decrease in RVC release rate (1.5 fold, P < 0.001) from liposomes. RVCLUV presented reduced cytotoxicity (P < 0.001) when compared with RVCPLAIN. Treatment with RVCLUV increased the duration (P < 0.001) and intensity of the analgesic effects either on sciatic nerve blockade (1.4–1.6 fold) and infraorbital nerve blockade tests (1.5 fold), in relation to RVCPLAIN. Regarding histological analysis, no morphological tissue changes were detected in the area of injection and sparse inflammatory cells were observed in only one of the animals treated with RVCPLAIN or RVCluv at 0.5%. Despite the differences between these preclinical studies and clinical conditions, we suggest RVCLUV as a potential new formulation, since RVC is a new and safe local anaesthetic agent. [ABSTRACT FROM AUTHOR]