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Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (−)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.

The assessment of ricinoleic acid (RA) incorporated into polymeric nanoparticles is a challenge that has not yet been explored. This bioactive compound, the main component of castor oil, has attracted attention in the pharmaceutical field for its valuable anti-inflammatory, antifungal, and antimicrobial properties. This work aims to develop a new and simple analytical method using high-performance liquid chromatography with diode-array detection (HPLC-DAD) for the identification and quantification of ricinoleic acid, with potential applicability in several other complex systems. The method was validated through analytical parameters, such as linearity, limit of detection and quantification, accuracy, precision, selectivity, and robustness. The physicochemical properties of the nanocapsules were characterized by dynamic light scattering (DLS) to determine their hydrodynamic mean diameter, polydispersity index (PDI), and zeta potential (ZP), via transmission electron microscopy (TEM) and quantifying the encapsulation efficiency. The proposed analytical method utilized a mobile phase consisting of a 65:35 ratio of acetonitrile to water, acidified with 1.5% phosphoric acid. It successfully depicted a symmetric peak of ricinoleic acid (retention time of 7.5 min) for both the standard and the RA present in the polymeric nanoparticles, enabling the quantification of the drug loaded into the nanocapsules. The nanocapsules containing ricinoleic acid (RA) exhibited an approximate size ranging from 309 nm to 441 nm, a PDI lower than 0.2, ζ values of approximately −30 mV, and high encapsulation efficiency (~99%). Overall, the developed HPLC-DAD procedure provides adequate confidence for the identification and quantification of ricinoleic acid in PLGA nanocapsules and other complex matrices.

Leishmaniasis is recognised as the second largest parasitic disease worldwide and yet a neglected disease. The current pharmacological treatments are associated with significant challenges, including high toxicity, high cost and parasitic resistance. Considering the potential of isopentyl caffeate (ICaf) as an anti-leishmanial agent, the present work evaluated the in vivo toxicity of ICaf and the absorption, distribution, metabolism, and excretion (ADME) properties in silico, aiming at the treatment of Leishmania amazonensis. For the in vivo toxicity testing, Swiss mice (Mus musculus) were treated with a single dose of ICaf. During the 14-day evaluation period, the animals underwent assessments including hippocratic screening, weight measurement, as well as histological and hematological evaluations. Analysis of ADME properties of ICaf was conducted to evaluate its pharmacokinetic characteristics and bioavailability. Characteristics, such as molar refractivity through Lipinski's Rule of Five, were identified. The in silico results showed that ICaf is considered to have good oral bioavailability and has potential to be considered as a new drug. From the in vivo toxicity testing, none of the evaluated parameters revealed toxicity of ICaf to the animals when treated intraperitoneally. The in vivo treatment reduced the lesion and the parasite load at the tested doses, corroborating the assumption that ICaf may be a potential pharmacological alternative against L. amazonensis.

Cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (ML) show clinical spectra that can range from a localized lesion (with a spontaneous healing process) to cases that progress to a generalized systemic disease with a risk of death. The treatment of leishmaniasis is complex since most of the available drugs show high toxicity. The development of an effective topical drug formulation for CL and ML treatment offers advantages as it will improve patient’s compliance to the therapy given the possibility for self-administration, as well as overcoming the first pass metabolism and the high costs of currently available alternatives. The most common dosage forms include solid formulations, such as membranes and semi-solid formulations (e.g., ointments, creams, gels, and pastes). Topical treatment has been used as a new route of administration for conventional drugs against leishmaniasis and its combinations, as well as to exploit new substances. In this review, we discuss the advantages and limitations of using topical drug delivery for the treatment of these two forms of leishmaniasis and the relevance of combining this approach with other pharmaceutical dosage forms. Emphasis will also be given to the use of nanomaterials for site-specific delivery.

Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy.

The skin is a complex and multifunctional organ, in which the static versus dynamic balance is responsible for its constant adaptation to variations in the external environment that is continuously exposed. One of the most important functions of the skin is its ability to act as a protective barrier, against the entry of foreign substances and against the excessive loss of endogenous material. Human skin imposes physical, chemical and biological limitations on all types of permeating agents that can cross the epithelial barrier. For a molecule to be passively permeated through the skin, it must have properties, such as dimensions, molecular weight, pKa and hydrophilic-lipophilic gradient, appropriate to the anatomy and physiology of the skin. These requirements have limited the number of commercially available products for dermal and transdermal administration of drugs. To understand the mechanisms involved in the drug permeation process through the skin, the approach should be multidisciplinary in order to overcome biological and pharmacotechnical barriers. The study of the mechanisms involved in the permeation process, and the ways to control it, can make this route of drug administration cease to be a constant promise and become a reality. In this work, we address the physicochemical and biopharmaceutical aspects encountered in the pathway of drugs through the skin, and the potential added value of using solid lipid nanoparticles (SLN) and nanostructured lipid vectors (NLC) to drug permeation/penetration through this route. The technology and architecture for obtaining lipid nanoparticles are described in detail, namely the composition, production methods and the ability to release pharmacologically active substances, as well as the application of these systems in the vectorization of various pharmacologically active substances for dermal and transdermal applications. The characteristics of these systems in terms of dermal application are addressed, such as biocompatibility, occlusion, hydration, emollience and the penetration of pharmacologically active substances. The advantages of using these systems over conventional formulations are described and explored from a pharmaceutical point of view.

Abstract Background Cryopreservation of stallion spermatozoa tends to cause plasma membrane damage due to the low ratio of cholesterol to phospholipids. Gums have been suggested as an alternative cryoprotectant to glycerol for stallion spermatozoa. Therefore, the present experiment was designed to verify whether the effect of addition of cashew gum (CG), or nanoparticles (NP) containing CG, to the extender before cooling on sperm quality in stallion semen. Ejaculates from 6 stallions were extended and split between six treatment groups (control, a-tocopherol [TOC], CG1, CG0.5, NP1 and NP0.5), stored in cryotubes at 4 °C. Results Aliquots were analysed by computer-assisted sperm motility analysis on the day of collection, and after 24 h and 48 h of cold storage. After 48 h, the total motility with NP1 (78.53 + 6.31%) was similar to control 85.79 + 6.31% at 0 h. The same pattern was observed for progressive motility. Membrane integrity assessed by flow cytometer was similar between control, TOC and G1 at all storage times. The DNA fragmentation in the control group increased at all time points, whereas chromatin integrity was maintained after 24 h in TOC and NP0.5 compared to 0 h. There was no increase in the proportion of live spermatozoa producing hydrogen peroxide, but there was a tendency for an increased proportion of spermatozoa in the live superoxide category in CG1 after 24 h cooled storage. Conclusions The addition of CG or CG-derived NP to extender for stallion semen was not harmful to the sperm cells.

The aim of this study was the development of a cereal bar based on bee pollen (BP), honey (H), and flour by-products (peel passion fruit flour—PPFF), generating an innovative product. BP is a protein-rich ingredient and can be used in the composition of cereal bars. PPFF is a by-product rich in fibers. The formulations were developed using a 23 factorial design with four replicates in the center point, studying the sensory analysis as a response variable. The texture and nutritional parameters were performed for the optimal formulation. BP showed ca. 15% of protein. The final formulation (10.35% BP, 6.8% PPFF, and 25% H) presented 22.2% moisture, 1.8% ash, 0.4% total fat, 3.0% fiber, 63.1% carbohydrates, and 74.0 Kcal/25 g. The sensory analysis presented valued around 7 (typical of a traditional bar). Regarding the possibility of purchasing the product, 51% of the panelists said they would probably buy the developed product. The formulated cereal bar had a similar composition as those already marketed. Moreover, it can be considered a source of fiber and is sensory acceptable. This approach opens up new opportunities for developing nutritional and functional foodstuff with improved sensorial aspects.

Wounds result from different causes (e.g., trauma, surgeries, and diabetic ulcers), requiring even extended periods of intensive care for healing, according to the patient’s organism and treatment. Currently, wound dressings generated by polymeric fibers at micro and nanometric scales are promising for healing the injured area. They offer great surface area and porosity, mimicking the fibrous extracellular matrix structure, facilitating cell adhesion, migration, and proliferation, and accelerating the wound healing process. Such properties resulted in countless applications of these materials in biomedical and tissue engineering, also as drug delivery systems for bioactive molecules to help tissue regeneration. The techniques used to engineer these fibers include spinning methods (electro-, rotary jet-), airbrushing, and 3D printing. These techniques have important advantages, such as easy-handle procedure and process parameters variability (type of polymer), but encounter some scalability problems. RJS is described as a simple and low-cost technique resulting in high efficiency and yield for fiber production, also capable of bioactive agents’ incorporation to improve the healing potential of RJS wound dressings. This review addresses the use of RJS to produce polymeric fibers, describing the concept, type of configuration, comparison to other spinning techniques, most commonly used polymers, and the relevant parameters that influence the manufacture of the fibers, for the ultimate use in the development of wound dressings.

The insect Plutella xylostella is known worldwide to cause severe damage to brassica plantations because of its resistance against several groups of chemicals and pesticides. Efforts have been conducted to overcome the barrier of P. xylostella genetic resistance. Because of their easy production and effective insecticidal activity against different insect orders, silver nanoparticles are proposed as an alternative for agricultural pest control. The use of entomopathogenic fungi for nanoparticle production may offer additional advantages since fungal biomolecules may synergistically improve the nanoparticle’s effectiveness. The present study aimed to synthesize silver nanoparticles using aqueous extracts of Beauveria bassiana, Metarhizium anisopliae, and Isaria fumosorosea isolates and to evaluate their insecticidal activity against P. xylostella, as innovative nano-ecofriendly pest control. The produced silver nanoparticles were evaluated by measuring the UV–vis spectrum and the mean particle size by dynamic light scattering (DLS). I. fumosorosea aqueous extract with 3-mM silver nitrate solution showed the most promising results (86-nm mean diameter and 0.37 of polydispersity). Scanning electron microscopy showed spherical nanoparticles and Fourier-Transform Infrared Spectroscopy revealed the presence of amine and amide groups, possibly responsible for nanoparticles’ reduction and stabilization. The CL50 value of 0.691 mg mL−1 was determined at 72-h for the second-instar larvae of the P. xylostella, promoting a 78% of cumulative mortality rate after the entire larval stage. From our results, the synthesis of silver nanoparticles mediated by entomopathogenic fungi was successful in obtaining an efficient product for insect pest control. The I. fumosorosea was the most suitable isolate for the synthesis of silver nanoparticles contributing to the development of a green nanoproduct and the potential control of P. xylostella.

Biosensor-integrated drug delivery systems are innovative devices in the health area, enabling continuous monitoring and drug administration. The use of smart polymer, bioMEMS, and electrochemical sensors have been extensively studied for these systems, especially for chronic diseases such as diabetes mellitus, cancer and cardiovascular diseases as well as advances in regenerative medicine. Basically, the technology involves sensors designed for the continuous analysis of biological molecules followed by drug release in response to specific signals. The advantages include high sensitivity and fast drug release. In this work, the main advances of biosensor-integrated drug delivery systems as new biomedical materials to improve the patients’ quality of life with chronic diseases are discussed.

Hydrogels are a great ally in the pharmaceutical and biomedical areas. They have a three-dimensional polymeric structure that allows the swelling of aqueous fluids, acting as an absorbent, or encapsulating bioactive agents for controlled drug release. Interestingly, plants are a source of biogels, specifically polysaccharides, composed of sugar monomers. The crosslinking of these polymeric chains forms an architecture similar to the extracellular matrix, enhancing the biocompatibility of such materials. Moreover, the rich hydroxyl monomers promote a hydrophilic behavior for these plant-derived polysaccharide gels, enabling their biodegradability and antimicrobial effects. From an economic point of view, such biogels help the circular economy, as a green material can be obtained with a low cost of production. As regards the bio aspect, it is astonishingly attractive since the raw materials (polysaccharides from plants-cellulose, hemicelluloses, lignin, inulin, pectin, starch, guar, and cashew gums, etc.) might be produced sustainably. Such properties make viable the applications of these biogels in contact with the human body, especially incorporating drugs for controlled release. In this context, this review describes some sources of plant-derived polysaccharide gels, their biological function, main methods for extraction, remarkable applications, and properties in the health field.

Natural polysaccharides are structures composed of highly diversified biological macromolecules whose properties have been exploited by a diversity of industries. Until 2018, the polysaccharides market raised more than US $ 12 billion worldwide, while an annual growth forecast of 4.8% is expected by 2026. The food industry is largely responsible for the consumption of this plant-source material, produced by microbiological fermentation. Among the used polysaccharides, gums are hydrocolloids obtained from a variety of sources and in different forms, being composed of salts of calcium, potassium, magnesium and sugar monomers. Their non-toxicity, hydrophilicity, viscosity, biodegradability, biocompatibility and sustainable production are among their main advantages. Although Brazil is amongst the largest producers of cashew gum, reaching 50 tons per year, the polysaccharide is not being used to its full potential, in particular, with regard to its uses in pharmaceuticals. Cashew gum (CG), obtained from Anacardium occidentale L., caught the attention of the industry only in 1970; in 1990, its production started to grow. Within the Brazilian academy, the groups from the Federal University of Ceará and Piauí are devoting the most efforts to the study of cashew gum, with a total of 31 articles already published. The number of patents in the country for innovations containing cashew tree gum has reached 14, including the technological process for the purification of cashew tree gum, comparison of physical and chemical methods for physicochemical characterizations, and optimum purification methodology. This scenario opens a range of opportunities for the use of cashew gum, mainly in the development of new pharmaceutical products, with a special interest in nanoparticles.

The increased mortality rates associated with antibiotic resistance has become a significant public health problem worldwide. Living beings produce a variety of endogenous compounds to defend themselves against exogenous pathogens. The knowledge of these endogenous compounds may contribute to the development of improved bioactive ingredients with antimicrobial properties, useful against conventional antibiotic resistance. Cowpea is an herbaceous legume of great interest due to its high protein content and high productivity rates. The study of genetic homology of vicillin (7S) from cowpea (Vigna unguiculata L.) with vicilins from soybean and other beans, such as adzuki, in addition to the need for further studies about potential biological activities of this vegetable, led us to seek the isolation of the vicilin fraction from cowpea and to evaluate the potential in vitro inhibitory action of pathogenic microorganisms. The cowpea beta viginin protein was isolated, characterized, and hydrolyzed in silico and in vitro by two enzymes, namely, pepsin and chymotrypsin. The antimicrobial activity of the protein hydrolysate fractions of cowpea flour was evaluated against Staphylococcus aureus and Pseudomonas aeruginosa, confirming the potential use of the peptides as innovative antimicrobial agents.

Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for several applications in the biomedical field, from therapeutics to diagnostics. Green nanocomposites stand for nanoparticles of biocompatible, biodegradable and non-toxic profiles. When using metal nanoparticles for drug delivery, the question of how hazardous these “virus-sized particles” can be is posed, due to their nanometer size range with enhanced reactivity compared to their respective bulk counterparts. These structures exhibit a high risk of being internalized by cells and interacting with the genetic material, with the possibility of inducing DNA damage. The Comet Assay, or Single-Cell Gel Electrophoresis (SCGE), stands out for its capacity to detect DNA strand breaks in eukaryotic cells. It has huge potential in the genotoxicity assessment of nanoparticles and respective cells’ interactions. In this review, the Comet assay is described, discussing several examples of its application in the genotoxicity evaluation of nanoparticles commonly administered in a set of routes (oral, skin, inhaled, ocular and parenteral administration). In the nanoparticles boom era, where guidelines for their evaluation are still very limited, it is urgent to ensure their safety, alongside their quality and efficacy. Comet assay or SCGE can be considered an essential tool and a reliable source to achieve a better nanotoxicology assessment of metal nanoparticles used in drug delivery.

Every year, more than thirty thousand tons of Cashew gum (Anacardium occidentale, family: Anacardiaceae) are produced in Brazil; however, only a small amount is used for different applications in foodstuff and in pharmaceutical industries. As a raw material for the production of drug delivery systems, cashew gum is still regarded as an innovative compound worth to be exploited. In this work, cashew gum was extracted from the crude exudate of cashew tree employing four methodologies resulting in a light brown powder in different yields (40.61% to 58.40%). The total ashes (0.34% to 1.05%) and moisture (12.90% to 14.81%) were also dependent on the purification approach. FTIR spectra showed the typical bands of purified cashew gum samples, confirming their suitability for the development of a pharmaceutical product. Cashew gum nanoparticles were produced by nanoprecipitation resulting in particles of low polydispersity (

Photodynamic therapy is one of the more unique cancer treatment options available in today’s arsenal against this devastating disease. It has historically been explored in cutaneous lesions due to the possibility of focal/specific effects and minimization of adverse events. Advances in drug delivery have mostly been based on biomaterials, such as liposomal and hybrid lipoidal vesicles, nanoemulsions, microneedling, and laser-assisted photosensitizer delivery systems. This review summarizes the most promising approaches to enhancing the photosensitizers’ transdermal delivery efficacy for the photodynamic treatment for cutaneous pre-cancerous lesions and skin cancers. Additionally, discussions on strategies and advantages in these approaches, as well as summarized challenges, perspectives, and translational potential for future applications, will be discussed.

Silver nanoparticles are widely used in the biomedical and agri-food fields due to their versatility. The use of biological methods for the synthesis of silver nanoparticles has increased considerably due to their feasibility and high biocompatibility. In general, microorganisms have been widely explored for the production of silver nanoparticles for several applications. The objective of this work was to evaluate the use of entomopathogenic fungi for the biological synthesis of silver nanoparticles, in comparison to the use of other filamentous fungi, and the possibility of using these nanoparticles as antimicrobial agents and for the control of insect pests. In addition, the in vitro methods commonly used to assess the toxicity of these materials are discussed. Several species of filamentous fungi are known to have the ability to form silver nanoparticles, but few studies have been conducted on the potential of entomopathogenic fungi to produce these materials. The investigation of the toxicity of silver nanoparticles is usually carried out in vitro through cytotoxicity/genotoxicity analyses, using well-established methodologies, such as MTT and comet assays, respectively. The use of silver nanoparticles obtained through entomopathogenic fungi against insects is mainly focused on mosquitoes that transmit diseases to humans, with satisfactory results regarding mortality estimates. Entomopathogenic fungi can be employed in the synthesis of silver nanoparticles for potential use in insect control, but there is a need to expand studies on toxicity so to enable their use also in insect control in agriculture.

Multi-Walled Carbon Nanotubes (MWCNT) have been functionalized with rutin through three steps (i. reaction step; ii. purification step; iii. drying step) and their physicochemical properties investigated with respect to morphological structure, thermal analysis, Fourier Transform Infrared Spectroscopy (FTIR), and cytotoxicity. The molecular docking suggested the rutin-functionalized MWCNT occurred by hydrogen bonds, which was confirmed by FTIR assays, corroborating the results obtained by thermal analyses. A tubular shape, arranged in a three-dimensional structure, could be observed. Mild cytotoxicity observed in 3T3 fibroblasts suggested a dose–effect relationship after exposure. These findings suggest the formation of aggregates of filamentous structures on the cells favoring the cell penetration.

Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.

The therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility to brain targets. The aim was to develop a liposomal formulation as ghrelin carrier. The quality by design (QbD) approach was used as a strategy for method development. The initial risk assessments were carried out using a fishbone diagram. A screening design study was performed for the critical material attributes/critical process parameters (CMAs/CPPs) on critical quality attributes (CQAs). Liposomes were obtained by hydrating phospholipid films, followed by extrusion or homogenization, and coated with chitosan. The optimized liposome formulation was produced by high-pressure homogenization coated with chitosan, and the resulted were liposomes size 72.25 ± 1.46 nm, PDI of 0.300 ± 0.027, the zeta potential of 50.3 ± 1.46 mV, and encapsulation efficiency of 53.2%. Moreover, chitosan coating improved performance in ex vivo permeation and mucoadhesion analyzes when compared to the uncoated liposome. In this context, chitosan coating is essential for the performance of the formulations in the ex vivo permeation and mucoadhesion analyzes. The intranasal administration of ghrelin liposomes coated with chitosan offers an innovative opportunity to treat cachexia.

Abstract INTRODUCTION: Leishmaniasis is a global public health concern. Currently available treatments are associated with considerable side effects. The use of nanotechnology has shown promise for improving efficacy and bioavailability and minimizing side effects. METHODS: This study investigated available literature, including patents and scientific articles, to identify advances in the use of nanotechnology for the treatment of leishmaniasis. RESULTS: Our findings revealed a stable number of patents and scientific articles published over the past five years. CONCLUSIONS: There is a need to intensify research on the use of nanotechnology for the treatment of leishmaniasis.

Chitosan films have been extensively studied as dressings in formulations for the treatment of chronic wounds. The incorporation of aloe vera (Aloe barbadensis Miller) into chitosan dressings could potentialize the healing process since aloe vera shows several pharmacological activities. This work aimed to evaluate the effect of aloe vera and chitosan concentrations on the physicochemical properties of the developed films. The films were obtained by casting technique and characterized with respect to their color parameters, morphology, barrier and mechanical properties, and thermal analysis. Results showed that the presence of aloe vera modified the films′ color parameters, changed barrier properties, increased fluid handling capacity (FHC), and decreased water-vapor permeability (WVP). The reduced elongation at break resulted in more rigid films. Aloe vera concentration did not significantly change film properties, but the presence of this gel increased the films’ stability at temperatures below 200 °C, showing similar behavior as chitosan films above 400 °C. The results suggest a crosslinking/complexation between chitosan and aloe vera, which combine appropriate physicochemical properties for application as wound dressing materials.

Leishmaniasis is one of the deadliest neglected tropical diseases affecting 12–15 million people worldwide, especially in middle- and low-income countries. Rapid and accurate diagnosis of the disease is important for its adequate management and treatment. Several techniques are available for the diagnosis of leishmaniasis. Among these, parasitological and immunological tests are most widely used. However, in most cases, the utilized diagnostic techniques are not good enough, showing cross-reactivity and reduced accuracy. In recent years, many new methods have been reported with potential for improved diagnosis. This review focuses on the diagnosis of Leishmania exploring the biosensors and nanotechnology-based options for their detection. New developments including the use of nanomaterials as fluorophores, fluorescence quenchers as reducing agents and as dendrimers for signal improvement and amplification, together with the use of aptamers to replace antibodies are described. Future research opportunities to overcome the current limitations on the available diagnostic approaches are also discussed.

Entomopathogenic fungi are microbial agents of insect control in nature. They have been used as biologic strategies to manage insect invasion; however, the challenge is to maintain their shelf life and viability when exposed to high temperatures, ultraviolet radiation, and humidity. Synthesized silver nanoparticles (AgNPs) from fungal extracellular enzymes are an alternative using these microorganisms to obtain nanoparticles with insecticidal action. The present study evaluates the biomass production and the potential to synthesize silver nanoparticles using entomopathogenic fungi isolates. Sixteen isolates of entomopathogenic fungi were used in this study. The fungi pathogenicity and virulence were evaluated using the insect model Tenebrio molitor, at a concentration of 5 × 106 conidia/mL. The fungal biomass was produced in a liquid medium, dried, and weighed. The synthesis of silver nanoparticles was performed with aqueous extracts of the entomopathogenic fungi and silver nitrate solution (1 mM), following characterization by a UV/vis spectrophotometer, mean size, and polydispersity index. The results showed a significant variation in pathogenicity, virulence, and biomass production among the evaluated fungi isolates; however, only one of the isolates did not have the potential to synthesize silver nanoparticles. Pearson’s correlation showed significant correlation values only between virulence × biosynthesis potential and biomass production × biosynthesis potential, both with negative values, indicating an inverse correlation. Thus, AgNPs with entomopathogenic fungus extract can produce an innovative bioinsecticide product using a green production process.

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with β-cyclodextrin (β-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and β-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the β-CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the β-cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/β-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/β-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.

O Imposto Territorial Rural (ITR) é um tributo de competência da União, e 50% de sua arrecadação deve ser transferido ao município de origem. Entretanto, existe a possibilidade de esse município apropriar-se de 100% da receita desde que assine um convênio com a Receita Federal e passe a ser o agente fiscalizador do tributo. Nesse sentido, na presente pesquisa teve-se por objetivo analisar a arrecadação do ITR nos municípios de Minas Gerais nos anos 2011 e 2012, fazendo uma comparação entre os municípios conveniados e os que não são. Além disso, buscou-se identificar os impactos na arrecadação após o município aderir ao convênio. Metodologicamente foram utilizados os testes de Mann Whitney e o teste T de Student para amostras emparelhadas. Os resultados indicaram que, de maneira geral, os municípios conveniados possuem arrecadação superior aos municípios não conveniados. Entretanto, ao se analisar a arrecadação dos municípios antes e depois de aderirem ao convênio, ficou constatado que mesmo aumentando a média de arrecadação essa diferença não foi estatisticamente significativa, uma vez que se verificam alguns municípios que diminuíram a arrecadação do ITR após aderirem ao convênio. Palavras-chave: Imposto Territorial Rural. Convênio. Arrecadação. Decentralization of the rural land tax: a study applied to the municipalities of Minas Gerais Abstract The Rural Land Tax (ITR) is a tribute competence of the Union, and 50% of its revenues must be transferred to the county of origin, however, there is a possibility of that municipality appropriate 100% of the revenue from signing an agreement with the Federal Revenue and becoming the supervisory agent of the tax. In this sense, in the present study one aimed to analyze the collection of the ITR in the municipalities of Minas Gerais in the years 2011 and 2012, making a comparison between the insured and the non-insured municipalities. In addition, it was sought to identify the impacts on the revenue after the municipality joining the agreement. Methodologically we used the Mann Whitney test and the Student t test for paired samples. The results indicated that, in general, the insured municipalities have higher revenues than the non-insured ones, however, when analyzing the collection of municipalities before and after joining the agreement, it was found that even increasing the average revenue this difference was not statistically significant, once there are some municipalities that decreased the collection of ITR after joining the agreement. Keywords: Rural Land Tax. Agreement. Collection.

Passiflora alata or passion fruit is a native flowering plant from Amazon, geographically spread from Peru to Brazil. The plant has long been used in folks medicine for its pharmacological properties and is included in the Brazilian Pharmacopoeia since 1929. The aim of this study was to evaluate the potential cytotoxic and antitumor activities of Passiflora alata leaf extract (PaLE) in S180-tumor bearing mice. The percentage of cell proliferation inhibition (% CPI) and IC50 in relation to 4 tumor cell lines were determined in PC3, K-562, HepG2 and S180 cell lines using the MTT assay. PaLE showed a CPI > 75% and greater potency (IC50 < 30 µg/mL) against PC3 and S180 cell lines. PaLE showed antitumor activity in treatments intraperitoneally (36.75% and 44.99% at doses of 100 and 150 mg/kg/day, respectively). Toxicological changes were shown in the reduced body mass associated with reduced food consumption, increased spleen mass associated with histopathological increase in the white pulp of the spleen and increased number of total leukocytes with changes in the percentage relationship between lymphocytes and neutrophils. Our outcomes corroborate the conclusion that PaLE has antitumor activity in vitro and in vivo with low toxicity.

The retina is a highly organized structure that is considered to be "an approachable part of the brain." It is attracting the interest of development scientists, as it provides a model neurovascular system. Over the last few years, we have been witnessing significant development in the knowledge of the mechanisms that induce the shape of the retinal vascular system, as well as knowledge of disease processes that lead to retina degeneration. Knowledge and understanding of how our vision works are crucial to creating a hardware-adaptive computational model that can replicate retinal behavior. The neuronal system is nonlinear and very intricate. It is thus instrumental to have a clear view of the neurophysiological and neuroanatomic processes and to take into account the underlying principles that govern the process of hardware transformation to produce an appropriate model that can be mapped to a physical device. The mechanistic and integrated computational models have enormous potential toward helping to understand disease mechanisms and to explain the associations identified in large model-free data sets. The approach used is modulated and based on different models of drug administration, including the geometry of the eye. This work aimed to review the recently used mathematical models to map a directed retinal network.

Multi-walled carbon nanotubes functionalized with naringenin have been developed as new drug carriers to improve the performance of lung cancer treatment. The nanocarrier was characterized by Transmission Electron Microscopy (TEM), Fourier-Transform Infrared Spectroscopy (FTIR), X-ray photoelectron spectroscopy, Raman Spectroscopy, and Differential Scanning Calorimetry (DSC). Drug release rates were determined in vitro by the dialysis method. The cytotoxic profile was evaluated using the MTT assay, against a human skin cell line (hFB) as a model for normal cells, and against an adenocarcinomic human alveolar basal epithelial (A569) cell line as a lung cancer in vitro model. The results demonstrated that the functionalization of carbon nanotubes with naringenin occurred by non-covalent interactions. The release profiles demonstrated a pH-responsive behavior, showing a prolonged release in the tumor pH environment. The naringenin-functionalized carbon nanotubes showed lower cytotoxicity on non-malignant cells (hFB) than free naringenin, with an improved anticancer effect on malignant lung cells (A549) as an in vitro model of lung cancer.

Sage species belong to the family of Labiatae/Lamiaceae and are diffused worldwide. More than 900 species of sage have been identified, and many of them are used for different purposes, i.e., culinary uses, traditional medicines and natural remedies and cosmetic applications. Another use of sage is the application of non-distilled sage extracts and essential oils to control phytopathogenic bacteria and fungi, for a sustainable, environmentally friendly agriculture. Biocidal propriety of non-distilled extracts and essential oils of sage are w documented. Antimicrobial effects of these sage extracts/essential oils depend on both sage species and bacteria and fungi species to control. In general, it is possible to choose some specific extracts/essential oils to control specific phytopathogenic bacteria or fungi. In this context, the use of nanotechnology techniques applied to essential oil from salvia could represent a future direction for improving the performance of eco-compatible and sustainable plant defence and represents a great challenge for the future.

Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 23 factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C).

Carnitine can be considered a conditionally essential nutrient for its importance in human physiology. This paper provides an updated picture of the main features of carnitine outlining its interest and possible use. Particular attention has been addressed to its beneficial properties, exploiting carnitine’s properties and possible use by considering the main in vitro, in animal, and human studies. Moreover, the main aspects of carnitine-based dietary supplements have been indicated and defined with reference to their possible beneficial health properties.

Medicinal plants, many of which are wild, have recently been under the spotlight worldwide due to growing requests for natural and sustainable eco-compatible remedies for pathological conditions with beneficial health effects that are able to support/supplement a daily diet or to support and/or replace conventional pharmacological therapy. The main requests for these products are: safety, minimum adverse unwanted effects, better efficacy, greater bioavailability, and lower cost when compared with synthetic medications available on the market. One of these popular herbs is hawthorn (Crataegus spp.), belonging to the Rosaceae family, with about 280 species present in Europe, North Africa, West Asia, and North America. Various parts of this herb, including the berries, flowers, and leaves, are rich in nutrients and beneficial bioactive compounds. Its chemical composition has been reported to have many health benefits, including medicinal and nutraceutical properties. Accordingly, the present review gives a snapshot of the in vitro and in vivo therapeutic potential of this herb on human health.

A new method based on reverse-phase HPLC combined with photodiode array (PDA) was developed to quantify the release of trans-resveratrol (tRES) from solid lipid nanoparticles (SLN). The mobile phase was composed of 75:0:25 (V/V) water/methanol/acetonitrile at 0−3.5 min, 32.5:30.0:37.5 (V/V) water/methanol/acetonitrile at 3.6−5.8 min, and 75:0:25 (V/V) water/methanol/acetonitrile at 5.9−10 min. The flow rate was set at 1.0 mL/min, and tRES was detected at the wavelength of 306.6 nm. A concentration range of 1−100 µg/mL was used to obtain the linear calibration curve. SLN were produced by ultrasound technique to load 0.1% (wt/wt) of tRES, and the in vitro release of the drug was run in modified Franz diffusion cells. The mean recovery of tRES was found to be 96.84 ± 0.32%. The intra-assay and inter-assay coefficients of variation were less than 5%. The proposed method was applied to in vitro permeability studies, and the Weibull model was found to be the one that best fits the tRES release, which is characterized by a simultaneous lipid chain relaxation and erosion during drug release.

Bupropion is an antidepressant used in the treatment of smoking. The purpose of this study was to prepare controlled-release hydrogel films for buccal administration of bupropion and investigate its physicochemical and cytotoxic properties. The films were prepared from ultrapure sodium carboxymethylcellulose, hydroxypropylmethylcellulose K4M, and medium-viscosity chitosan. Evaluation of film physicochemical characteristics was based on scanning electron microscopy, bupropion content, mechanical strength (burst strength, relaxation, resilience, and traction), and cytotoxicity. Bupropion content in bilayer films was 121 mg per 9 cm2. The presence of bupropion modified film mechanical strength, but did not compromise the use of this pharmaceutical form. As shown by the cytotoxicity results, films containing bupropion did not cause cellular damage. Bupropion administration in the form of hydrogel films is a potentially useful alternative in the treatment of smoking.

Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to produce micro/nanoparticles with a narrow size distribution and high encapsulation efficiency. The aim of this work was to produce cetyl palmitate SLNs using SCF to be loaded with praziquantel (PZQ) as an insoluble model drug. The mean particle size (nm), polydispersity index (PdI), zeta potential, and encapsulation efficiency (EE) were determined on the freshly prepared samples, which were also subject of Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), drug release profile, and in vitro cytotoxicity analyses. PZQ-SLN exhibited a mean size of ~25 nm, PdI ~ 0.5, zeta potential ~−28 mV, and EE 88.37%. The DSC analysis demonstrated that SCF reduced the crystallinity of cetyl palmitate and favored the loading of PZQ into the lipid matrices. No chemical interaction between the PZQ and cetyl palmitate was revealed by FTIR analysis, while the release or PZQ from SLN followed the Weibull model. PZQ-SLN showed low cytotoxicity against fibroblasts cell lines. This study demonstrates that SCF may be a suitable scale-up procedure for the production of SLN, which have shown to be an appropriate carrier for PZQ.

Biopolymeric films with silver sulfadiazine (AgSD) are proposed as an alternative to the occlusive AgSD-containing creams and gauzes, which are commonly used in the treatment of conventional burns. While the recognized cytotoxicity of AgSD has been reported to compromise its use as an antimicrobial drug in pharmaceuticals, this limitation can be overcome by developing sustained-release formulations. Microporous materials as zeolites can be used as drug delivery systems for sustained release of AgSD. The purpose of this work was the development and characterization of chitosan/zeolite composite films to be used as wound dressings. Zeolite was impregnated with AgSD before the production of the composite films. The physicochemical properties of zeolites and the films were evaluated, as well as the antimicrobial activity of the polymeric films and the cytotoxicity of the films in fibroblasts Balb 3T3/c. Impregnated zeolite exhibited changes in FTIR spectra and XRD diffraction patterns, in comparison to non-impregnated composites, which corroborate the results obtained with EDX-SEM. The pure chitosan film was compact and without noticeable defects and macropores, while the film with zeolite was opaquer, more rigid, and efficient against Candida albicans and some gram-negative bacteria. The safety evaluation showed that although the AgSD films present cytotoxicity, they could be used in a concentration-dependent fashion.

The objective of this work was to characterize the toxicological profile of a newly developed sunscreen formulation based on polymeric nanocapsules (NCs) loading benzophenone-3 (BZP3). NCs composed of poly(ε-caprolactone) carrot oil and Pluronic® F68 were produced by emulsification-diffusion method. Their mean particle size (Z-Ave) ranged from 280 to 420 nm, polydispersity index (PDI) was below 0.37, while zeta potential (ZP) reached about |+11 mV|. No cytotoxic effects were observed in L929 fibroblast cell line for the blank (i.e., non-loaded) NCs and BZP3-loaded NCs (BZP3-NCs). The semi-solid sunscreen formulation was stable over time (centrifugation testing) and exhibited non-Newtonian pseudoplastic behavior, which is typical of products for topical application onto the skin. The sun protection factor (SPF) value reached 8.84, when incorporating BZP3-NCs (SPF of 8.64) into the semi-solid formulation. A synergistic effect was also observed when combining the formulation ingredients of nanocapsules, i.e., SPF of carrot oil was 6.82, blank NCs was 6.84, and BZP3-loaded NCs was 8.64. From the hen’s egg-chorioallantoic membrane test (HET-CAM) test, the non-irritation profile of the developed formulations could also be confirmed. The obtained results show a promising use of poly(ε-caprolactone) nanocapsules to be loaded with lipophilic sunscreens as benzophenone-3.

The incidence of neglected diseases in tropical countries, such as Leishmaniasis and Chagas’s disease, is attributed to a set of biological and ecological factors associated with the socioeconomic context of developing countries and with a significant burden to health care systems. Both Leishmaniasis and Chagas’s disease are caused by different protozoa and develop diverse symptoms, which depend on the specific species infecting man. Currently available drugs to treat these disorders have limited therapeutic outcomes, frequently due to microorganisms’ drug resistance. In recent years, significant efforts have been made towards the development of innovative drug delivery systems aiming to improve bioavailability and pharmacokinetic profiles of classical drug therapy. This paper discusses the key facts of Leishmaniasis and Chagas’s disease, the currently available pharmacological therapies and the new drug delivery systems for conventional drugs.

The present work reports the effect of polysaccharides (chitosan and sodium alginate) on silica nanoparticles (SiNP) for hydrophilic molecules delivery taking insulin as model drug. The influence of tetraethyl orthosilicate (TEOS) and homogenization speed on SiNP properties was assessed by a 22 factorial design achieving as optimal parameters: 0.43 mol/L of TEOS and homogenization speed of 5000 rpm. SiNP mean particle size (Z-Ave) was of 256.6 nm and polydispersity index (PI) of 0.218. SiNP coated with chitosan (SiNP-CH) or sodium alginate (SiNP-SA) increased insulin association efficacy; reaching 84.6% (SiNP-SA) and 90.8% (SiNP-CH). However, coated SiNP released 50−60% of the peptide during the first 45 min at acidic environment, while uncoated SiNP only released ~30%. Similar results were obtained at pH 6.8. The low Akaike’s (AIC) values indicated that drug release followed Peppas model for SiNP-SA and second order for uncoated SiNP and SiNP-CH (pH 2.0). At pH 6.8, the best fitting was Boltzmann for Ins-SiNP. However, SiNP-CH and SiNP-SA showed a first-order behavior. Cytotoxicity of nanoparticles, assessed in Caco-2 and HepG2 cells, showed that 100 to 500 µg/mL SiNP-CH and SiNP-SA slightly decreased cell viability, comparing with SiNP. In conclusion, coating SiNP with selected polysaccharides influenced the nanoparticles physicochemical properties, the insulin release, and the effect of these nanoparticles on cell viability.

Dibucaine (DBC) is among the more potent long-acting local anesthetics (LA), and it is also one of the most toxic. Over the last decades, solid lipid nanoparticles (SLN) have been developed as promising carriers for drug delivery. In this study, SLN formulations were prepared with the aim of prolonging DBC release and reducing its toxicity. To this end, SLN composed of two different lipid matrices and prepared by two different hot-emulsion techniques (high-pressure procedure and sonication) were compared. The colloidal stability of the SLN formulations was tracked in terms of particle size (nm), polydispersity index (PDI), and zeta potential (mV) for 240 days at 4 °C; the DBC encapsulation efficiency was determined by the ultrafiltration/centrifugation method. The formulations were characterized by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and release kinetic experiments. Finally, the in vitro cytotoxicity against 3T3 fibroblast and HaCaT cells was determined, and the in vivo analgesic action was assessed using the tail flick test in rats. Both of the homogenization procedures were found suitable to produce particles in the 200 nm range, with good shelf stability (240 days) and high DBC encapsulation efficiency (~72⁻89%). DSC results disclosed structural information on the nanoparticles, such as the lower crystallinity of the lipid core vs. the bulk lipid. EPR measurements provided evidence of DBC partitioning in both SLNs. In vitro (cytotoxicity) and in vivo (tail flick) experiments revealed that the encapsulation of DBC into nanoparticles reduces its intrinsic cytotoxicity and prolongs the anesthetic effect, respectively. These results show that the SLNs produced are safe and have great potential to extend the applications of dibucaine by enhancing its bioavailability.

The purpose of this work was to introduce a new concept of coated pellets containing chitosan microspheres loaded with didadosine for oral administration, aiming at reducing the frequency of administration and improving the bioavailability by a suitable release profile. Chitosan microspheres were produced under fluidized bed, followed by extrusion and spheronization to obtain pellets with a mean diameter of about 1 mm. The pellets were then coated with Kollidon® VA64 and Kollicoat® MAE100P in water dispersion to depict a sustained release profile. Conventional hard gelatine capsules were loaded with these pellets and tested in vitro for their release profile of didadosine. Dissolution testing confirmed that chitosan microsphere pellets provides appropriate sustained release up to 2 h behavior for didanosine. Keywords: Didanosine, Pellets, Gastro-resistance, Coating, Microspheres, Chitosan

Nanopartículas poliméricas produzidas a partir de polímeros pré-formados, como os poliésteres alifáticos, têm sido amplamente utilizadas para incorporar, principalmente, princípios ativos lipofílicos. A produção das nanopartículas (nanocápsulas e nanosferas) por polímeros pré-formados pode ser realizada por emulsificação-evaporação do solvente, por deslocamento do solvente, por salting-out ou por emulsificação-difusão do solvente. Estes métodos de produção estão revisados e descritos neste artigo, evidenciando os parâmetros tecnológicos que interferem nas características físico-químicas das nanopartículas, como a solubilidade do princípio ativo, o volume e pH do meio de polimerização, a massa molar e concentração do monômero e a natureza e concentração do tensoativo.Polymeric nanoparticles have been produced by pre-formed polymers using aliphatic polyesters, which have been widely used to incorporate lipophilic drugs. The production of nanoparticles (nanospheres and nanocapsules) by pre-formed polymers can be performed by emulsification-solvent evaporation, solvent replacement, salting out or by emulsification-solvent diffusion. These methods are reviewed and discussed in this article, highlighting the technological parameters that influence the physicochemical characteristics of nanoparticles, such as the solubility of drug, the volume and pH of polymerization, the molecular weight and monomer concentration and the nature and concentration of the surfactant.

Poorly soluble drugs have low bioavailability, representing a major challenge for the pharmaceutical industry. Processing drugs into the nanosized range changes their physical properties, and these are being used in pharmaceutics to develop innovative formulations known as Nanocrystals. Use of nanocrystals to overcome the problem of low bioavailability, and their production using different techniques such as microfluidization or high pressure homogenization, was reviewed in this paper. Examples of drugs, cosmetics and nutraceutical ingredients were also discussed. These technologies are well established in the pharmaceutical industry and are approved by the Food and Drug Administration.

Nanopartículas poliméricas produzidas a partir de polímeros sintéticos, como copolímeros do ácido metacrílico, ésteres acrílicos ou metacrílicos, têm sido amplamente utilizadas na área farmacêutica para encapsulação de princípios ativos. Essas nanopartículas apresentam as vantagens de proteção, liberação controlada, melhor biodisponibilidade e menor toxicidade, proporcionando maior conforto aos pacientes e adesão ao tratamento. A produção das nanopartículas (nanocápsulas e nanosferas) por polimerização de monômeros é revisada e descrita neste artigo, evidenciando os parâmetros tecnológicos que interferem nas características físico-químicas das nanopartículas, como a solubilidade do princípio ativo, o volume e pH do meio de polimerização, a massa molar e concentração do monômero e a natureza e concentração do tensoativo.Polymeric nanoparticles obtained from synthetic polymers such as copolymers of methacrylic acid, acrylic esters or metacrylics, have been widely used in pharmaceuticals for encapsulation of drugs. These nanoparticles have the advantages of drug protection, controlled release, improved bioavailability and lower toxicity, resulting in greater comfort to patients and compliance to the treatment. The production of nanoparticles (nanospheres and nanocapsules) by polymerization of monomers is reviewed and discussed in this article, highlighting the technological parameters that affect the physicochemical characteristics of nanoparticles, e.g. drug solubility, phase volume, pH of polymerization, molecular weight and monomer concentration, and the nature and concentration of the surfactant.

Micropartículas produzidas a partir de polímeros sintéticos têm sido amplamente utilizadas na área farmacêutica para encapsulação de princípios ativos. Essas micropartículas apresentam as vantagens de proteção do princípio ativo, mucoadesão e gastrorresistência, melhor biodisponibilidade e maior adesão do paciente ao tratamento. Além disso, utiliza menores quantidade de princípio ativo para obtenção do efeito terapêutico proporcionando diminuição dos efeitos adversos locais, sistêmicos e menor toxidade. Os polímeros sintéticos empregados na produção das micropartículas são classificados biodegradáveis ou não biodegradáveis, sendo os biodegradáveis mais utilizados por não necessitam ser removidos cirurgicamente após o término de sua ação. A produção das micropartículas poliméricas sintéticas para encapsulação tanto de ativos hidrofílicos quanto hidrofóbicos pode ser emulsificação por extração e/ou evaporação do solvente; coacervação; métodos mecânicos e estão revisados neste artigo evidenciando as vantagens, desvantagens e viabilidade de cada metodologia. A escolha da metodologia e do polímero sintético a serem empregados na produção desse sistema dependem da aplicação terapêutica requerida, bem como a simplicidade, reprodutibilidade e factibilidade do aumento de escala da produção.Microparticles produced from synthetic polymers have been widely used in the pharmaceutical field for encapsulation of drugs. These microparticles show several advantages such as drug protection, mucoadhesion, gastro-resistance, improved bioavailability and increased patient's compliance. In addition, it is possible to use lower amount of drug to achieve therapeutic efficiency with reduced local/systemic adverse side effects and low toxicity. Synthetic polymers used for the production of microparticles are classified as biodegradable or non-biodegradable, being the former more popular since these do not need to be removed after drug release. Production of polymeric microparticles can be used for encapsulation of hydrophilic and hydrophobic drugs, by emulsification following solvent extraction/evaporation, coacervation, methods that are revised in this paper, including advantages, disadvantages and viability of each methodology. Selection of methodology and synthetic polymer depends of the therapeutic purpose, as well as simplicity, reproducibility and possibility to scale up.

Os diferentes sistemas de transporte têm evidenciado potencial terapêutico para uma grande variedade de princípios ativos, satisfazendo vários requisitos, como a prevenção da sua eliminação rápida do organismo, a redução da sua toxicidade sistêmica, a estabilização e a otimização do seu metabolismo, e o direcionamento específico ao local alvo e os mecanismos de defesa. No entanto, têm sido reconhecidos vários outros desafios associados à liberação específica do princípio ativo ao local alvo, pelo que, para ultrapassar os obstáculos químicos e biológicos, a seleção do polímero utilizado para a preparação do sistema de transporte é de importância crucial. O presente trabalho apresenta um relato sobre os principais polímeros naturais e sintéticos utilizados para a preparação de sistemas de transporte de princípios ativos in vivo.The different carrier systems have shown therapeutic potential for a wide variety of drugs, satisfying multiple requirements, such as prevention of rapid elimination, reducing toxicity, promoting stabilization, optimization of metabolism, drug delivery and defense mechanisms. However, it has been recognized several other challenges associated with the specific release of actives in drug delivery. Therefore, to overcome chemical and biological obstacles, the selection of the polymer used to prepare the transport system is crucial. This paper presents a report on the main natural and synthetic polymers used in the preparation of drug carrier systems in vivo.

Solid lipid nanoparticles have been extensively investigated as drug delivery systems. These colloidal systems have major advantages compared to others more traditional. Reported advantages include sustained release, ability to solubilize lipophilic drugs, increased physical and chemical stability of labile molecules, decreased unwanted side-effects showing lower toxicity, and scale up facilities. This paper aims at reviewing the traditional methods of solid lipid nanoparticles production, such as fusion-emulsification (hot and cold), solvent evaporation-emulsification and microemulsion, dealing with the main technological parameters that influence the quality properties of solid lipid nanoparticles.

FAS/FASL altered expression may cause tumor protecting immunomodulation, with a direct impact on patient prognosis. FAS expression was studied in 60 squamous cell carcinomas of the oral cavity. FAS expression did not show a significant association with tumor histopathological characteristics, but was significantly associated with lymph node positivity. FAS expression was significantly associated with disease specific death and negative FAS expression was an independent risk factor, increasing risk 4 times when compared to positive expression. When FAS and FASL expression results were combined, we were able to define high, intermediate and low risk profiles. Disease-free and disease-specific survival were significantly correlated with FAS/FASL expression profiles. The high risk category was an independent marker for earlier disease relapse and disease-specific death, with approximately 4- and 6-fold increased risk, respectively, when compared to the low risk profile. Risk profiles based on FAS/FASL expression showed that high risk was significantly associated with increased disease relapse and death, as well as shorter disease-free or disease-specific survival. This categorization, added to patient clinical data, may facilitate the choice of therapy, minimizing treatment failure and increasing disease control.