Novel pMDI formulations for pulmonary delivery of proteins

In this paper, we demonstrate that co-spray-drying a model protein with sodium carboxymethylcellulose (NaCMC) protects protein integrity during spray-drying, and that the resultant spray-dried powders can be successfully dispersed in hydrofluoroalkane (HFA) propellant to prepare pressurised metered dose (pMDI) formulations that exhibit high respirable fractions. The spray-dried powders were formulated as HFA-134a pMDI suspensions in the absence of any other excipients (e.g. surfactants) or co-solvents (e.g. ethanol). The in vitro aerosolisation profile of these systems was assessed using the twin stage impinger; fine particle fractions (FPF) ≥50% of the recovered dose were obtained. Following storage for five months, the aerosolisation performance was reassessed; the NaCMC-free formulation demonstrated a significant decrease in FPF, whereas the performance of the NaCMC-modified formulations was statistically equivalent to their initial performance. Thus, formulation of pMDI suspensions using NaCMC-based spray-dried powders is a promising approach for the pulmonary delivery of proteins and peptides. © 2009 Elsevier B.V. All rights reserved.

Biomimetic synthetic lubricants (Biosurfactants)

Poly(styrene-co-maleic anhydride) (PSMA) based copolymers are known to undergo conformational transition in response to environmental stimuli. This smart behaviour makes it possible to mimic the behaviour of native apoproteins. The primary aim of this study was to develop a better understanding of the structure-property relationships of various PSMA-based copolymers sought. The work undertaken in this thesis has revealed that the responsive behaviour of PSMA-based copolymers can be tailored by varying the molecular weight, hydrophobic (styrene) and hydrophilic (maleic acid) balance, and more so in the presence of additional hydrophobic, mono-partial ester moieties. Novel hydrophilic and hydrophobic synthetic surfactant protein analogues have successfully been prepared. These novel lipid solubilising agents possess a broad range of HLB (hydrophilic-lipophilic balance) values that have been estimated. NMR spectroscopy was utilised to confirm the structures for PSMA-based copolymers sought and proved useful in furthering understanding of the structure-property relationships of PSMA-based copolymers. The association of PSMA with the polar phospholipid, 2-dilauryl-sn-glycero-3- phosphocholine (DLPC) produces polymer-lipid complexes analogous to lipoprotein assemblies present in the blood plasma. NMR analysis reveals that the PSMA-based copolymers are not perfectly alternating. Regio-irregular structures, atactic and random monomer sequence distribution have been identified for all materials studied. Novel lipid solubilising agents (polyanionic surfactants) have successfully been synthesised from a broad range of PSMA-based copolymers with desired estimated HLB values that interact with polar phospholipids (DLPC/DPPC) uniquely. Very low static and dynamic surface tensions have been observed via the du Noϋy ring method and Langmuir techniques and correlate well with the estimated HLB values. Synthetic protein-lipid analogues have been successfully synthesised, that mimic the unique surface properties of native biological lubricants without the use of solvents. The novel PSMA-DLPC complexes have successfully been combined with hyaluronan (hyaluronic acid, HA). Today, the employment of HA is economically feasible, because it is readily available from bacterial fermentation processes in a thermally stable form - HyaCare®. The work undertaken in this thesis highlights the usage of HA in biolubrication applications and how this can be optimised and thus justified by carefully selecting the biological source, concentration, molecular weight, purity and most importantly by combining it with compatible boundary lubricating agents (polar phospholipids). Experimental evidence supports the belief that the combined HA and PSMA-DLPC complexes provide a balance of rheological, biotribological and surface properties that are composition dependent, and show competitive advantage as novel synthetic biological lubricants (biosurfactants).

Self-assembled SnO2 micro- and nanosphere-based gas sensor thick films from an alkoxide-derived high purity aqueous colloid precursor

Tin oxide is considered to be one of the most promising semiconductor oxide materials for use as a gas sensor. However, a simple route for the controllable build-up of nanostructured, sufficiently pure and hierarchical SnO2 structures for gas sensor applications is still a challenge. In the current work, an aqueous SnO2 nanoparticulate precursor sol, which is free of organic contaminants and sorbed ions and is fully stable over time, was prepared in a highly reproducible manner from an alkoxide Sn(OR)4 just by mixing it with a large excess of pure neutral water. The precursor is formed as a separate liquid phase. The structure and purity of the precursor is revealed using XRD, SAXS, EXAFS, HRTEM imaging, FTIR, and XRF analysis. An unconventional approach for the estimation of the particle size based on the quantification of the Sn-Sn contacts in the structure was developed using EXAFS spectroscopy and verified using HRTEM. To construct sensors with a hierarchical 3D structure, we employed an unusual emulsification technique not involving any additives or surfactants, using simply the extraction of the liquid phase, water, with the help of dry butanol under ambient conditions. The originally generated crystalline but yet highly reactive nanoparticles form relatively uniform spheres through self-assembly and solidify instantly. The spheres floating in butanol were left to deposit on the surface of quartz plates bearing sputtered gold electrodes, producing ready-for-use gas sensors in the form of ca. 50 μm thick sphere-based-films. The films were dried for 24 h and calcined at 300°C in air before use. The gas sensitivity of the structures was tested in the temperature range of 150-400°C. The materials showed a very quickly emerging and reversible (20-30 times) increase in electrical conductivity as a response to exposure to air containing 100 ppm of H2 or CO and short (10 s) recovery times when the gas flow was stopped.

Matrix-assisted diffusion-ordered spectroscopy

Diffusion NMR is a potentially routine tool in the analysis of mixtures, from industrial and synthetic outputs to natural products. However, the technique struggles to resolve species of similar size. Matrix-assisted DOSY offers a flexible approach to resolving such ambiguities on the basis of the chemical structures involved and on their interactions with a larger co-solute or matrix. The use of chromatographic supports, surfactants and polymers, in particular, is illustrated. The resolution of a wide range of different analyte mixtures, on the basis of differences in chemical structure and in stereochemistry, is demonstrated.

Condensation-enhanced self-assembly as a route to high surface area α-aluminas

High surface area nanosized α-alumina has been obtained by thermally treating a sol-gel-derived mesophase at 1200 C; the mesophase was synthesized by a sol-gel route involving evaporation induced self-assembly (EISA) of a hydrolyzed gel from Al-tri-sec-butoxide in s-BuOH in the presence of a nonionic surfactant (EO20PO70EO20), HCl as catalyst, and water (H2O/Al = 6). The activated material renders moderate surface areas of about 8.4-10 m2 g-1, associated with significant crystallite coarsening. The key aspect to produce smaller crystallites is making the mesophase more resistant to coarsening. This was achieved by enhancing the condensation step by treating the hydrolyzed gel with tetrabutyl ammonium hydroxide (TBAOH) before evaporation. The characteristics of the mesophase indicate condensation of the primary particles with less AlO5 unsaturated sites, at the expense of a lower solid yield due to small crystallites dissolution. The activated TBAOH condensed EISA material is composed of α-alumina aggregated crystallites of about 60-100 nm, and the material possesses surface areas ranging from 16 to 24 m2 g -1 due to the improved resistance to coarsening. At least two aspects are suggested to play a role in this. The worm-hole morphology of the mesophase aggregates yields high particle coordination, which favors densification rather than coarsening. Furthermore, the decrease of the AlO5 defect sites by the TBAOH condensation makes the mesophase less reactive and consequently more resistant to coarsening. © 2013 American Chemical Society.

Surfactant solubilization and subsequent bioavailability of phenanthrene

Contamination of soil, sediment and groundwater by hydrophobic organic compounds (HOCs) is a matter of growing concern because groundwater is a valuable and limited resource, and because such contamination is difficult to address. This investigation involved an experimental evaluation of the addition of several surfactant solutions to aqueous and soil-water systems contaminated with phenanthrene, a selected HOC. The results are presented in terms of: * phenanthrene solubilization achieved through surfactant addition * observed effects of surfactant addition on the mineralization of phenanthrene * estimation of relative toxicities of various surfactants using toxicity assays * literature-reported biodegradability/persistence of selected surfactants * surfactant sorption/precipitation onto soil and its impacts on proposed use of surfactant-amended remediation Surfactants were observed to facilitate the transfer of phenanthrene from the soil-sorbed phase to the aqueous pseudophase, however, surfactant solubilization did not translate into enhanced phenanthrene biodegradation.

Obtenção de organovermiculitas utilizando tensoativos e microemulsões e suas aplicações na separação de isômeros do Xileno

Surfactants are versatile organic compounds that have, in a single molecule, double chemical affinity. The surfactant molecule is composed by a hy drophobic tail group, a hydrocarbon chain (linear, branched, or mixed), and by a hydrophilic head group, which contains polar groups that makes it able to be applied in the organophilization process of natural clays. Microemulsions are microheterogeneous b lends composed by: a surfactant, an oily phase (non - polar solvent), an aqueous phase, and, sometimes, a co - surfactant (short - chain alcohol). They are systems with thermodynamic stability, transparent, and have high solubility power. Vermiculite is a clay m ineral with an expandable crystalline structure that has high cation exchange capacity. In this work vermiculite was used to obtain organoclays. The ionic surfactants dodecyl ammonium chlori de (DDAC) and cetyltrimethylammonium bromide (C 16 TAB) were used in the organophilization process. They were used as surfactant aqueous solutions and, for DDAC, as a microemulsion system. The organoclays were used to promote the separation of binary mixtures of xylene isomers (ortho - and meta - xylene). Dif ferent analytical techniques were used to characterize microemulsion systems and also the nanoclays. It was produced a water - rich microemulsion system with 0.92 nm droplet average diameter. The vermiculite used in this work has a cationic exchange capacity of 172 meq/100g and magnesium as main cation (24.25%). The basal spacing of natural vermiculite and organo - vermiculites were obtained by X - ray Diffraction technique. The basal spacing was 1.48nm for natural vermiculite, 4.01nm for CTAB - vermiculite (CTAB 4 ) , and 3.03nm for DDAC - vermiculite (DDAC M1A), that proves the intercalation process. Separation tests were carried out in glass columns using three binary mixtures of xylene (ortho - xylene and meta - xylene). The results showed that the organovermiculite pre sented an enhanced chemical affinity by the mixture of hydrocarbons, when compared with the natural vermiculite, and also its preference by ortho - xylene. A factorial experimental design 2 2 with triplicate at the central point was used to optimize the xylen e separation process. The experimental design revealed that the initial concentration of isomers in the mixture and the mass of organovermiculite were the significant factors for an improved separation of isomers. In the experiments carried out using a bin ary mixture of ortho - xylene and meta - xylene (2:1), after its percolating through the organovermiculite bed (DDAC M1), it was observed the preference of the organoclay by the ortho - xylene isomer, which was retained in greater quantity than the meta - xylene o ne. At the end of the treatment, it was obtained a final concentration in meta - xylene of 47.52%.

Estudo comparativo de diferentes sistemas de injeção de vapor aplicados à remediação de solos contaminados por diesel

Among the potentially polluting economic activities that compromise the quality of soil and groundwater stations are fuel dealers. Leakage of oil derived fuels in underground tanks or activities improperly with these pollutants can contaminate large areas, causing serious environmental and toxicological problems. The number of gas stations grew haphazardly, without any kind of control, thus the environmental impacts generated by these enterprises grew causing pollution of soil and groundwater. Surfactants using various techniques have been proposed to remedy this kind of contamination. This study presents innovation as the application of different systems containing surfactant in the vapor phase and compares their diesel removal efficiencies of soil containing this contaminant. For this, a system that contains seven injection wells the following vaporized solutions: water, surfactant solution, microemulsion and nanoemulsion, The surfactants used were saponified coconut oil (OCS), in aqueous solution and an ethoxylated alcohol UNTL-90: aqueous solution , and nanoemulsion and microemulsion systems. Among the systems investigated, the nanoemulsion showed the highest efficiency, achieving 88% removal of residual phase diesel, the most ecologically and technically feasible by a system with lower content of active matter

Expressão heteróloga de biossurfactantes identificados em bibliotecas metagenômicas

The microorganisms have a vast genetic diversity and they are present throughout the biosphere, however, only about 1% of the species can be cultivated by traditional cultivation techniques. Within this diversity there is a huge pool genetic and biological being explored. The metagenomics has enabled direct access to microbial genome derived from environmental samples using independent methods of cultivation. The methodology enables to obtain functional information about the proteins, as well as identify potential products with biotechnological interest and new industrially exploitable biological resources, such as new solutions to environmental impacts. Oil-contaminated areas are characterized by a large accumulation of hydrocarbons and surfactants may be used for bioremediation. Thus, the metagenomic approach was used in this study in order to select genes involved in the degradation and hydrocarbon emulsification. In a previous work, the environmental DNA (eDNA) was extracted from soil samples collected from two different areas (Caatinga and Saline River) of Rio Grande do Norte (Brazil), the metagenomic libraries were constructed and functionally analyzed. The clone able to degrade the oil was evaluated for the ability to synthesize biosurfactants. The sequence analysis revealed an ORF with 897 bp, 298 amino acids and a protein with around 34 kDa. The search for homology in GenBank revealed sequence similarity with a hypothetical protein of representatives Halobacteriaceae family, who were recently shown as strains producing biosurfactants. The presence of the inserted coding sequence and the acquired phenotype was confirmed. Primers were designed and the ORF amplified by PCR. The ORF was subcloned into pETDuet-1 expression vector for subsequent purification of the protein of interest containing a histidine tail. The tests performed to confirm the biosurfactant activity and the ability of hydrocarbon degradation showed positive results. The immunodetection test (western blot) using the monoclonal AntiHis® confirmed the presence of the environmental protein. This study was the first to report a possible protein with biosurfactant activity obtained from a metagenomic approach

Caracterização físico-química de sistemas micelares

The process of adsorption and micellization of the surfactants sodium dodecyl sulfate, dodecylammonium chloride and hexaethylene glycol mono-n-dodecyl ether in water-air interface has been studied using measurements of surface tension in aqueous media and NaCl 0.1 mol/L in temperatures of 25, 33 and 40 °C. From these data, critical micelle concentrations and thermodynamic parameters of micellization and adsorption were determined in order to elucidate the behaviors of micellization and adsorption for these surfactants in the proposed medium. For the determination of the thermodynamic parameters of adsorption we utilized the equations of isotherms of Langmuir and Gibbs. Γmáx values determined by the different equations were correlated to the explanation of results. Temperature and salinity were analyzed in terms of their influence on the micellization and adsorption process, and the results were explained based on intermolecular interactions. The values of Gmic have confirmed that the micelle formation for the surfactants studied occurs spontaneously

Desenvolvimento e avaliação tribológica de emulsão O/A a partir de óleo vegetal epoxidado para aplicação em fluídos de corte

The cutting fluids are lubricants used in machining processes, because they present many benefits for different processes. They have many functions, such as lubrication, cooling, improvement in surface finishing, besides they decreases the tool wear and protect it against corrosion. Therefore due to new environment laws and demand to green products, new cutting fluids must be development. These shall be biodegradable, non-toxic, safety for environment and operator healthy. Thus, vegetable oils are a good option to solve this problem, replacing the mineral oils. In this context, this work aimed to develop an emulsion cutting fluid from epoxidized vegetable oil, promoting better lubrication and cooling in machining processes, besides being environment friendly. The methodology was divided in five steps: first one was the biolubricant synthesis by epoxidation reaction. Following this, the biolubricant was characterized in terms of density, acidity, iodo index, oxirane index, viscosity, thermal stability and chemical composition. The third step was to develop an emulsion O/A with different oil concentration (10, 20 and 25%) and surfactant concentration (1, 2.5 and 5%). Also, emulsion stability was studied. The emulsion tribological performance were carried out in HFRR (High Frequency Reciprocating Rig), it consists in ball-disc contact. Results showed that the vegetable based lubricant may be synthesized by epoxidationreaction, the spectra showed that there was 100% conversion of the epoxy rings unsaturations. In regard the tribological assessment is observed that the percentage of oil present in the emulsion directly influenced the film formation and coefficient of friction for higher concentrations the film formation process is slow and unstable, and the coefficient of friction. The high concentrations of surfactants have not improved the emulsions tribological performance. The best performance in friction reduction was observed to emulsion with 10% of oil and 5% of surfactant, its average wear scar was 202 μm.

Novos adsorventes para aplicação na remoção de enxofre de combustíveis

Currently the market requires increasingly pure oil derivatives and, with that, comes the need for new methods for obtaining those products that are more efficient and economically viable. Considering the removal of sulfur from diesel, most refineries uses catalytic hydrogenation process, the hydrodesulfurization. These processes needs high energy content and high cost of production and has low efficiency in removing sulfur at low concentrations (below 500 ppm). The adsorption presents itself as an efficient and economically viable alternative in relation to the techniques currently used. With that, the main purpose of this work is to develop and optimize the obtaining of new adsorbents based on diatomite, modified with two non ionic surfactants microemulsions, adding efficiency to the material, to its application on removal of sulfur present in commercial diesel. Analyses were undertaken of scanning electron microscopy (SEM), x-ray diffraction (XRD), x-ray fluorescence (XRF), thermogravimetry (TG) and N2 adsorption (BET) for characterization of new materials obtained. The variables used for diatomite modification were: microemulsion points for each surfactant (RNX 95 and UNTL 90), microemulsion aqueous phase through the use or non-use of salts (CaCl2 and BaCl2), the contact time during the modification and the contact form. The study of adsorption capacity of materials obtained was performed using a statistical modeling to evaluate the influence of salt concentration in the aqueous phase (20 ppm to 1500 ppm), finite bath temperature (25 to 60° C) and the concentration of sulphur in diesel. It was observed that the temperature and the concentration of sulphur (300 to 1100 ppm) were the most significant parameters, in which increasing their values increase the ability of modified clay to adsorb the sulphur in diesel fuel. Adsorption capacity increased from 0.43 to mg/g 1.34 mg/g with microemulsion point optimization and with the addition of salts.

Remoção de corantes utilizando tensoativos: extração por ponto de nuvem e floculação iônica

The textile sector is one of the main contributors to the generation of industrial wastewaters due to the use of large volumes of water, which has a high organic load content. In these, it is observed to the presence of dyes, surfactants, starch, alcohols, acetic acid and other constituents, from the various processing steps of the textiles. Hence, the treatment of textile wastewater becomes fundamental before releasing it into water bodies, where they can cause disastrous physical-chemical changes for the environment. Surfactants are substances widely used in separation processes and their use for treating textile wastewaters was evaluated in this research by applying the cloud point extraction and the ionic flocculation. In the cloud point extraction was used as surfactant nonylphenol with 9.5 ethoxylation degree to remove reactive dye. The process evaluation was performed in terms of temperature, surfactant and dye concentrations. The dye removal reached 91%. The ionic flocculation occurs due to the presence of calcium, which reacts with anionic surfactant to form insoluble surfactants capable of attracting the organic matter by adsorption. In this work the ionic flocculation using base soap was applied to the treatment of synthetic wastewater containing dyes belonging to three classes: direct, reactive, and disperse. It was evaluated by the influence of the following parameters: surfactant and electrolyte concentrations, stirring speed, equilibrium time, temperature, and pH. The flocculation of the surfactant was carried out in two ways: forming the floc in the effluent itself and forming the floc before mixing it to the effluent. Removal of reactive and direct dye, when the floc is formed into textile effluent was 97% and 87%, respectively. In the case where the floc is formed prior to adding it to the effluent, the removal to direct and disperse dye reached 92% and 87%, respectively. These results show the efficience of the evaluated processes for dye removal from textile wastewaters.

Remoção de metais utilizando o hexadecanoato de sódio

Industrial activities like mining, electroplating and the oil extraction process, are increasing the levels of heavy metals such as Cu, Fe, Mg and Cd in aquatic ecosystems. This increase is related to the discharge of effluents containing trace of this elements above the maximum allowed by law. Methods such as ion exchange, membrane filtration and chemical precipitation have been studied as a means of treatment of these metals contamination. The precipitation of metals using anionic surfactants derived from carboxylic acids emerged as an alternative for the removal of metals from industrial effluents. The reaction between bivalent ions and these types of surfactants in aqueous solution leads to the formation of metal carboxylates, which can precipitate in the form of flakes and are subsequently removed by a process of decantation or simple filtration. In this work the metals extraction is performed by using the surfactant sodium hexadecanoate as extracting agent. The main purpose was to study the effect of temperature, solution pH, and concentration of surfactant in the metal removal process. The statistical design of the process showed that the process is directly dependent to changes in pH and concentration of surfactant, but inversely proportional and somewhat dependent to temperature variation, with the latter effect being considered negligible in most cases. The individual study of the effect of temperature showed a strong dependence of the process with the Kraft point, both for the surfactant used as extracting agent, as for the surfactant obtained after the reaction of this surfactant with the metal. From data of temperatures and concentrations of the surfactant was possible to calculate the equilibrium constant for the reaction between sodium hexadecanoate and copper ions. Later, thermodynamic parameters were determined, showing that the process is exothermic and spontaneous.

Remoção de corantes têxteis em solução aquosa utilizando bentonita natural e organofílica

Searches using organoclays have been the subject of great interest due to its wide application in industry and removal of environmental pollutants. The organoclays were obtained using bentonite (BEN) and cationic surfactants: hexadecyltrimethyl ammonium bromide (HDTMA-Br) and trimethyloctadecyl ammonium bromide (TMOA-Br) in ratios of 50 and 100 % of its ion exchange capacity. The materials were characterized by the techniques of X-ray diffraction (DRX), infrared spectroscopy (IR), X-ray fluorescence (FRX), thermal analysis (TA) and scanning electron microscopy (SEM). The bentonite and organobentonite were used on the adsorption of dyes, Remazol Blue RR (AZ) and Remazol Red RR (VM) in aqueous solution. The adsorption models of Langmuir and Freundlich were used for mathematical description of sorption equilibrium data and obtain the constants of the isotherms. The Freundlich model fit to the data for adsorption equilibrium of bentonite, on the other hand both the model fit to the Langmuir adsorption test of organoclays. The adsorption processes using adsorbents with both dyes interspersed with HDTMA-Br show endothermic and exothermic nature, respectively.