Topical foam as a promising carrier system for active pharmaceutical ingredients: review of clinical studies.

Skin disorders are preferentially treated by topical administration of medicines or cosmetics because of the possibility of local action. However, a great concern is the delivery of topical actives with effective penetration through the stratum corneum to ensure the desired effect. Considering the search for a carrier system that allows the penetration/permeation of active pharmaceutical ingredients through this structure, searching for effective topical pharmaceutical forms is needed. Foams have been widely studied over the years due to their high capacity to favor the active to overcome the cutaneous barrier and because this form of presentation has ease of application and high acceptability by users. The objective of this review was to analyze the potential of foam as a topical pharmaceutical form for treating skin disorders, upon clinical cases reported in the literature. Foam presents technical advantages when compared to other conventional topical pharmaceutical forms due to its fast action, high tolerance, and safety, with reduction or total remission of adverse events. Regarding the patient, foam increased the rate of adherence to the treatment. Therefore, it is concluded that foam is an effective, secure, and stable topical presentation form for carrying active pharmaceutical ingredients and widely accepted by patients.

Environmentally Friendly Strategies for Formulating Vegetable Oil-Based Nanoparticles for Anticancer Medicine.

The development of green synthesized polymeric nanoparticles with anticancer studies has been an emerging field in academia and the pharmaceutical and chemical industries. Vegetable oils are potential substitutes for petroleum derivatives, as they present a clean and environmentally friendly alternative and are available in abundance at relatively low prices. Biomass-derived chemicals can be converted into monomers with a unique structure, generating materials with new properties for the synthesis of sustainable monomers and polymers. The production of bio-based polymeric nanoparticles is a promising application of green chemistry for biomedical uses. There is an increasing demand for biocompatible and biodegradable materials for specific applications in the biomedical area, such as cancer therapy. This is encouraging scientists to work on research toward designing polymers with enhanced properties and clean processes, containing oncology active pharmaceutical ingredients (APIs). The nanoencapsulation of these APIs in bio-based polymeric nanoparticles can control the release of the substances, increase bioavailability, reduce problems of volatility and degradation, reduce side effects, and increase treatment efficiency. This review discusses the use of green chemistry for bio-based nanoparticle production and its application in anticancer medicine. The use of castor oil for the production of renewable monomers and polymers is proposed as an ideal candidate for such applications, as well as more suitable methods for the production of bio-based nanoparticles and some oncology APIs available for anticancer application.

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

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

Conventional and PEGylated Liposomes as Vehicles of Copaifera sabulicola.

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

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

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

Biosorption of heavy fuel oil from aqueous solution by Eichhornia crassipes (Mart.) Solms in natura.

This work investigated the efficiency of bioremediation of heavy fuel oil (HFO) in aqueous solutions by living Eichhornia crassipes (Mart.) Solms, also known as water hyacinth. Possibility of using post-biosorption macrophytes to produce briquettes was also studied. HFO was characterized by its density, viscosity, and Fourier-transform infrared spectroscopy. Water hyacinth was characterized by scanning electron microscope, pH of zero point of charge, buoyancy, and wettability. Experiments were performed to evaluate effects of contact time and initial oil concentration on biosorption. E. crassipes presented a hydrophobic nature, ideal for the treatment of oily effluents. Hollow structures in macrophytes were also identified, which favor capillary rise and retention of oils of high density and viscosity. Biosorption efficiency of HFO reached 94.8% in tests with initial concentration of 160 mg.L-1. A calorific value of 4022 kcal.kg-1 was obtained in briquettes made of water hyacinth post-biosorption. These results reinforce the great potential of E. crassipes as a sustainable and efficient alternative for treatment of oily effluents.

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

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

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

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

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

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

Opioid-based micro and nanoparticulate formulations: alternative approach on pain management.

CONTEXT: Opioids have been used as the reference treatment on chronic pain. However, they are related to serious adverse effects which affect the patient compliance to treatment, as well as, his quality of life. Particulate formulations have been investigated as an alternative to improve opioid efficacy and safety. OBJECTIVE: Summarise the available studies concerning micro and nanoencapsulated opioid formulations discussing their biopharmaceutical characteristics, such as composition, size, in vitro release, pharmacokinetic and antinociceptive profile. METHODS: Papers available in 1995-2015 at Medline, Science Direct and Web of Science databases were collected and assessed. Searches were performed using varied combinations of the keywords of this work. RESULTS: Opioid-loaded particles showed prolonged drug release with maintenance of serum therapeutic concentrations and extended analgesia when compared with the free drugs. The side effects incidences were reduced or maintained the same. CONCLUSION: Particulate formulations can significantly increase both potency and safety profiles of opioids.

Liposomes Size Engineering by Combination of Ethanol Injection and Supercritical Processing.

Supercritical fluid extraction using a high-pressure packed tower is proposed not only to remove the ethanol residue from liposome suspensions but also to affect their size and distribution leading the production of nanosomes. Different operating pressures, temperatures, and gas to liquid ratios were explored and ethanol was successfully extracted up to a value of 400 ppm; liposome size and distribution were also reduced by the supercritical processing preserving their integrity, as confirmed by Z-potential data and Trasmission Electron Microscopy observations. Operating at 120 bar and 38°C, nanosomes with a mean diameter of about 180 ± 40 nm and good storage stability were obtained. The supercritical processing did not interfere on drug encapsulation, and no loss of entrapped drug was observed when the water-soluble fluorescein was loaded as a model compound. Fluorescein encapsulation efficiency was 30% if pure water was used during the supercritical extraction as processing fluid; whereas an encapsulation efficiency of 90% was obtained if the liposome suspension was processed in water/fluorescein solution. The described technology is easy to scale up to an industrial production and merge in one step the solvent extraction, liposome size engineering, and an excellent drug encapsulation in a single operation unit.

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

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

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

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

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

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

Effects of temperature and salinity on the survival rates of coxicerberus ramosae (Albuquerque, 1978), an interstitial isopod of a Sandy Beach on the coast of Brazil

The tolerance to the combined effects of temperature and salinity was investigated in the interstitial isopod Coxicerberus ramosae (Albuquerque, 1978), a species of intertidal zone of sandy beaches in Rio de Janeiro, Brazil. The animals were collected on Praia Vermelha Beach. The experiments lasted 24 h and nine salinities and seven temperatures were used for a total of 63 combinations. Thirty animals were tested in each combination. The species showed high survival in most of the combinations. The temperature of 35 ºC was lethal and at 5 ºC, the animals tolerated only a narrow range of salinities. The statistical analyses showed that the effects of temperature and salinity were significant on the survival, which confirmed the euryhalinity and eurythermy of this species.

A resistência aos efeitos combinados de temperatura e salinidade foi investigada no isópode intersticial Coxicerberus ramosae (Albuquerque, 1978) encontrado comumente na zona intertidal de praias arenosas do Rio de Janeiro, Brasil. Os exemplares foram coletados na Praia Vermelha. Os experimentos tiveram a duração de 24 horas e nove salinidades e sete temperaturas foram utilizadas, perfazendo um total de 63 combinações. Em cada combinação de T e S foram testados 30 animais. A espécie mostrou um grande percentual de sobrevivência na maior parte das combinações. A temperatura de 35ºC foi letal e na temperatura de 5ºC a espécie resistiu a uma faixa estreita de salinidades. As análises estatísticas mostraram que tanto os efeitos da temperatura como da salinidade e da interação entre estes fatores foram significativos na sobrevivência da espécie.O alto percentual de sobrevivência da espécie nas diferentes combinações de temperatura e salinidade, confirma, portanto, a eurialinidade e a euritermia da espécie, características comuns das espécies intersticiais litorais.

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

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

Wittgenstein e Walter Benjamin: inquietações éticas e filosóficas como formas de viver e pensar / Wittgenstein and Walter Benjamin: ethical and philosophical considerations as ways of living and thinking

O artigo analisa a filosofia da linguagem e a ética em Wittgenstein e Walter Benjamin, tendo como propósito tornar consistentes as concepções teóricas que se aproximam, sem deixar, contudo, de enfatizar a especificidade inerente aos percursos do pensamento de cada um e os seus nítidos distanciamentos. Destaca-se o entendimento que ambos oferecem sobre as possibilidades de expandir os limites da linguagem como uma questão filosófica fundamental, apontando as conseqüências desta tentativa nas formas de viver e pensar.(AU)

The article analyses the philosophy of language and ethics in Wittgenstein and Walter Benjamin, and its goal is to make consistent the theoretical conceptions that approach each other emphasizing, however, the specificity inherent to the course of thought of each one of them and their clear differences. The understanding that both offer about the possibilities of expanding the limits of language as a fundamental philosophical matter is highlighted, pointing out the consequences of this effort in the ways of living and thinking.(AU)

Linguagem e experiência: singularidade do olhar para o contexto da escola a partir das contribuições de Wittgenstein e Bakhtin

Este trabalho teve como objetivo desenvolver o tema da experiência subjetiva como produção singular e inacabada a partir das contribuições de Wittgenstein e Bakhtin, dois filósofos da linguagem. Particularmente, os conceitos de ética e estética, no pensamento desses autores, permitiram expressar um modo de analisar a experiência no contexto da escola, além de enfrentar uma espécie de tensão na abordagem da singularidade da produção subjetiva e sua construção na linguagem como ação e reflexão.(AU)

Wittgenstein e Walter Benjamin: inquietações éticas e filosóficas como formas de viver e pensar / Wittgenstein and Walter Benjamin: ethical and philosophical considerations as ways of living and thinking

O artigo analisa a filosofia da linguagem e a ética em Wittgenstein e Walter Benjamin, tendo como propósito tornar consistentes as concepções teóricas que se aproximam, sem deixar, contudo, de enfatizar a especificidade inerente aos percursos do pensamento de cada um e os seus nítidos distanciamentos. Destaca-se o entendimento que ambos oferecem sobre as possibilidades de expandir os limites da linguagem como uma questão filosófica fundamental, apontando as conseqüências desta tentativa nas formas de viver e pensar.

The article analyses the philosophy of language and ethics in Wittgenstein and Walter Benjamin, and its goal is to make consistent the theoretical conceptions that approach each other emphasizing, however, the specificity inherent to the course of thought of each one of them and their clear differences. The understanding that both offer about the possibilities of expanding the limits of language as a fundamental philosophical matter is highlighted, pointing out the consequences of this effort in the ways of living and thinking.

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

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