17 resultados para L-LACTIC ACID

em Universidade Federal do Rio Grande do Norte(UFRN)


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The environmental impact caused by the disposal of non-biodegradable polymer packaging on the environment, as well as the high price and scarcity of oil, caused increase of searches in the area of biodegradable polymers from renewable resources were developed. The poly (lactic acid) (PLA) is a promising polymer in the market, with a large availability of raw material for the production of its monomer, as well as good processability. The aimed of this study was synthesis PLA by direct polycondesation of lactic acid, using the tool of experimental design (DOE) (central composite rotatable design (CCRD)) to optimize the conditions of synthesis. The polymer obtained was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), viscosimetric analysis, differential scanning calorimeter (DSC) and size exclusion chromatography (SEC). The results confirmed the formation of a poly (lactic acid) semicrystalline in the syntheses performed. Through the central composite rotatable design was possible to optimize the crystallization temperature (Tc) and crystallinity degree (Xc). The crystallization temperature maximum was found for percentage of catalyst around the central point (0,3 (%W)) and values of time ranging from the central point (6h) to the upper level (+1) (8h). The crystallization temperature maximum was found for the total synthesis time of 4h (-1) and percentage of catalyst 0,1(W%) (-1). The results of size exclusion chromatography (SEC) showed higher molecular weights to 0,3 (W%) percent of catalyst and total time synthesis of 3,2h

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The environmental impact caused by the disposal of non-biodegradable polymer packaging on the environment, as well as the high price and scarcity of oil, caused increase of searches in the area of biodegradable polymers from renewable resources were developed. The poly (lactic acid) (PLA) is a promising polymer in the market, with a large availability of raw material for the production of its monomer, as well as good processability. The aimed of this study was synthesis PLA by direct polycondesation of lactic acid, using the tool of experimental design (DOE) (central composite rotatable design (CCRD)) to optimize the conditions of synthesis. The polymer obtained was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), viscosimetric analysis, differential scanning calorimeter (DSC) and size exclusion chromatography (SEC). The results confirmed the formation of a poly (lactic acid) semicrystalline in the syntheses performed. Through the central composite rotatable design was possible to optimize the crystallization temperature (Tc) and crystallinity degree (Xc). The crystallization temperature maximum was found for percentage of catalyst around the central point (0,3 (%W)) and values of time ranging from the central point (6h) to the upper level (+1) (8h). The crystallization temperature maximum was found for the total synthesis time of 4h (-1) and percentage of catalyst 0,1(W%) (-1). The results of size exclusion chromatography (SEC) showed higher molecular weights to 0,3 (W%) percent of catalyst and total time synthesis of 3,2h

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With the advances in medicine, life expectancy of the world population has grown considerably in recent decades. Studies have been performed in order to maintain the quality of life through the development of new drugs and new surgical procedures. Biomaterials is an example of the researches to improve quality of life, and its use goes from the reconstruction of tissues and organs affected by diseases or other types of failure, to use in drug delivery system able to prolong the drug in the body and increase its bioavailability. Biopolymers are a class of biomaterials widely targeted by researchers since they have ideal properties for biomedical applications, such as high biocompatibility and biodegradability. Poly (lactic acid) (PLA) is a biopolymer used as a biomaterial and its monomer, lactic acid, is eliminated by the Krebs Cycle (citric acid cycle). It is possible to synthesize PLA through various synthesis routes, however, the direct polycondensation is cheaper due the use of few steps of polymerization. In this work we used experimental design (DOE) to produce PLAs with different molecular weight from the direct polycondensation of lactic acid, with characteristics suitable for use in drug delivery system (DDS). Through the experimental design it was noted that the time of esterification, in the direct polycondensation, is the most important stage to obtain a higher molecular weight. The Fourier Transform Infrared (FTIR) spectrograms obtained were equivalent to the PLAs available in the literature. Results of Differential Scanning Calorimetry (DSC) showed that all PLAs produced are semicrystalline with glass transition temperatures (Tgs) ranging between 36 - 48 °C, and melting temperatures (Tm) ranging from 117 to 130 °C. The PLAs molecular weight characterized from Size Exclusion Chromatography (SEC), varied from 1000 to 11,000 g/mol. PLAs obtained showed a fibrous morphology characterized by Scanning Electron Microscopy (SEM)

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Methotrexate (MTX) is a drug used in the chemotherapy of some kind of cancers, autoimmune diseases and non inflammatory resistant to corticosteroids uveits. However, the rapid plasmatic elimination limits its therapeutic success, which leads to administration of high doses to maintain the therapeutic levels in the target tissues, occurring potential side effects. The aim of this study was to obtain spray dried biodegradable poly-lactic acid co-glycolic acid (PLGA) microparticles containing MTX. Thus, suitable amounts of MTX and PLGA were dissolved in appropriate solvent system to obtain solutions at different ratios drug/polymer (10, 20, 30 and 50% m/m). The physicochemical characterizing included the quantitative analysis of the drug using a validate UV-VIS spectrophotometry method, scanning electron microscopy (SEM), infrared spectrophotometry (IR), thermal analyses and X-ray diffraction analysis. The in vitro release studies were carried out in a thermostatized phosphate buffer pH 7.4 (0.05 M KH2PO4) medium at 37°C ± 0.2 °C. The in vitro release date was subjected to different kinetics release models. The MTX-loaded PLGA microparticles showed a spherical shape with smooth surface and high level of entrapped drug. The encapsulation efficiency was greater then 80%. IR spectroscopy showed that there was no chemical bond between the compounds, suggesting just the possible occurrence of hydrogen bound interactions. The thermal analyses and X-ray diffraction analysis shown that MTX is homogeneously dispersed inside polymeric matrix, with a prevalent amorphous state or in a stable molecular dispersion. The in vitro release studies confirmed the sustained release for distinct MTX-loaded PLGA microparticles. The involved drug release mechanism was non Fickian diffusion, which was confirmed by Kornmeyer-Peppas kinetic model. The experimental results demonstrated that the MTX-loaded PLGA microparticles were successfully obtained by spray drying and its potential as prolonged drug release system.

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New drug delivery systems have been used to increase chemotherapy efficacy due the possible drug resistance of cancer cells. Poly (lactic acid) (PLA) microparticles are able to reduce toxicity and prolong methotrexate (MTX) release. In addition, the use of PLA/poloxamer polymer blends can improve drug release due to changes in the interaction of particles with biological surfaces. The aim of this study was developing spray dried biodegradable MTX-loaded microparticles and evaluate PLA interactions with different kinds of Pluronic® (PLUF127 and PLUF68) in order to modulate drug release. The variables included different drug:polymer (1:10, 1:4.5, 1:3) and polymer:copolymer ratios (25:75, 50:50, 75:25). The precision and accuracy of spray drying method was confirmed assessing drug loading into particles (75.0- 101.3%). The MTX/PLA microparticles showed spherical shape with an apparently smooth surface, which was dependent on the PLU ratio used into blends particles. XRD and thermal analysis demonstrated that the drug was homogeneously dispersed into polymer matrix, whereas the miscibility among components was dependent on the used polymer:copolymer ratio. No new drug- polymer bond was identified by FTIR analysis. The in vitro performance of MTX-loaded PLA microparticles demonstrated an extended-release profile fitted using Korsmeyer- Peppas kinetic model. The PLU accelerated drug release rate possible due PLU leached in the matrix. Nevertheless, drug release studies carried out in cell culture demonstrated the ability of PLU modulating drug release from blend microparticles. This effect was confirmed by cytotoxicity observed according to the amount of drug released as a function of time. Thus, studied PLU was able to improve the performance of spray dried MTX-loaded PLA microparticles, which can be successfully used as carries for modulated drug delivery with potential in vivo application

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Some fibrous materials, for having properties such as biocompatibility, strength and flexibility, are of great interest for medical and pharmaceutical applications. Among these materials, the fabric made from polylactic acid (PLA) has received special attention, and beside to present these features, is derived from biological source, antimicrobial and bioabsorbable. One of the limitations of PLA is its low wettability and capillarity. Due to this, it is necessary to perform surface modification of the knitted fabric, increasing its hydrophilicity. This work aims to realize the plasma treatment at low pressure in order to increase the surface energy of the polymer. The work was divided into three steps: i) Influence of the gas ratio (oxygen and nitrogen) in the surface modification of PLA fabric after the plasma treatment, ii) physical characterization and physicochemical surface tissue; iii) Evaluation of the effect from current and gas ratio in the capillary rise of tissues and iv) Study of capillarity in yarns and fabrics. The results showed that better gas ratios were the atmospheres: 100% oxygen; 100% nitrogen and 50% oxygen and 50% nitrogen. The surface characterization showed changes in topography and introduction of polar groups which increased the wettability of the fabric. In another part of this study, it was found that the atmosphere containing only nitrogen gas showed the most capillary rise to a current of 0.15 A. The results in capillary yarns and fabrics showed that the thread reached equilibrium in a time much less than the fabric to an atmosphere of 100% nitrogen and 0.15 A. Current Plasma technology was effective to increase the hydrophilicity of PLA fabric, providing surface characteristics favorable for future application in the biomedical field

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The dried beef is a food traditionally eaten by Northeastern and has an extensive trade in the city of Natal-RN. It is usually produced in an empirical manner, without any standardization in production. Characterized as partially dehydrated meat product, so that the activity of water present is not sufficient to prevent microbial growth, degradation or the production of microbial toxins. The guarantee that the market dried beef is to provide a quality product hygienic, microbiological, physicochemical and sensory stable and adequate for the safety and consumer satisfaction, which has been increasingly attracted to food with natural preservatives. Thus, the meat industries are replacing the current seasonings and natural preservatives for similar, with it without affecting the shelf life of products. Lactic acid has been used to meet these requirements. In this sense, this study aimed to evaluate the effect of lactic acid on the physico-chemical, microbiological and sensory, besides knowing the consumer profile of dried meat of the City of Natal / RN. The results demonstrated that the use of lactic acid in concentrations of 1% and 2% during the processing of dried meat, had statistically significant effect (p < 0.05) on the physico-chemical (pH and water activity) and consequently reduced the microbial count does not alter the taste of the new product developed. Regarding the results on the consumer profile, it was found that the majority of respondents (71.75%) did not observe the presence of the stamp of the Federal Inspection Service (SIF) to buy this meat food that 81.55% of consumers check the hygiene conditions of the site and handlers, however, a large proportion of respondents not concerned with the guarantee of origin of typical regional products featuring a hazard to food safety for consumers of the city of Natal-RN

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Volatile Organic Compounds are pollutants coming mainly from activities that use fossil fuels. Within this class are the BTEX (benzene, toluene, ethylbenzene and xylenes) compounds that are considered hazardous. Among the various existing techniques for degradation of pollutants, there is advanced oxidation using H2O2 generating hidoxil radical ( OH). In this work, the mesoporous material of MCM-41 was synthesized by hydrothermal method and then was used as support, the impregnation of titanium by the method of synthesis with excess solvent to obtain the catalyst Ti-MCM-41. The catalyst was used in the reaction catalyzed removal of BTEX in water using H2O2 as oxidant. The materials were characterized by: XRD, TG/DTG, FTIR, nitrogen adsorption-desorption and FRX-EDX, in order to verify the method of impregnation of the mesoporous titanium support was effective. Catalytic tests were carried out in reactors of 20 mL containing BTEX (100.0 μg/L), H2O2 (2.0 M) and Ti-MCM-41 (2.0 g/L) in acid medium. The reaction occurred for 5 h at 60 °C and analysis were performed by gas chromatography with photoionization detector and static headspace sampler. The characterizations have proven the effectiveness of the synthesis method used and the incorporation of titanium lt in the support. The catalytic tests showed satisfactory results with conversion of more than 95 % for the studied compounds, where the catalyst 48% Ti-MCM-41 showed a higher removal efficiency of the compounds under study

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Chemical modification of clays has been extremely studied in the search for improvements of their properties for use in various areas, such as in combating pollution by industrial effluents and dyes. In this work, the vermiculite was chemically modified in two ways, characterized and evaluated the adsorption of methylene blue dye. First was changed with the addition of a surfactant (hexadecyltrimethylammonium bromide, BHTA) making it an organophilic clay and then by adding an acid (HCl) by acid activation. Some analyzes were performed as X-ray fluorescence (FRX), X-ray diffraction (DRX), adsorption isotherms of methylene blue dye, infrared (FTIR) , scanning electron microscopy (SEM), thermal gravimetric analysis and spectroscopy energy dispersive (EDS). Analysis by FRX of natural vermiculite indicates that addition of silicon and aluminum, clay presents in its structure the magnesium, calcium and potassium with 16 % organic matter cations. The DRX analyzes indicated that the organic vermiculite was an insertion of the surfactant in the space between the lamellae, vermiculite and acid partial destruction of the structure with loss of crystallinity. The adsorption isotherms of methylene blue showed that there was a significant improvement in the removal of dye to the vermiculite with the addition of cationic surfactant hexadecyltrimethylammonium bromide and treatment with acid using HCl 2 mol/L. In acid vermiculites subsequently treated with surfactant, the adsorption capacity increased with respect to natural vermiculite, however was much lower compared vermiculite modified with acid and surfactant separately. Only the acidic vermiculite treated with surfactant adjusted to the Langmuir model. As in the infrared spectrometry proved the characteristics of natural vermiculite. In the organic vermiculite was observed the appearance of characteristic bands of CH3, CH2, and (CH3)4N. Already on acid vermiculite, it was realized a partial destruction with decreasing intensity of the characteristic band of vermiculite that is between 1074 and 952 cm-1. In the SEM analysis, it was observed that there was partial destruction to the acid treatment and a cluster is noted between the blades caused by the presence of the surfactant. The TG shows that the higher mass loss occurs at the beginning of the heating caused by the elimination of water absorbed on the surface between layers. In the organic vermiculite also observed a loss of mass between 150 and 300 °C caused decomposition of the alkylammonium molecules (surfactants)

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Chitosan is a biopolymer derived from the shells of crustaceans, biodegradable, inexpensive and renewable with important physical and chemical properties. Moreover, the different modifications possible in its chemical structure generate new properties, making it an attractive polysaccharide owing to its range of potential applications. Polymers have been used in oil production operations. However, growing concern over environmental constraints has prompted oil industry to search for environmentally sustainable materials. As such, this study sought to obtain chitosan derivatives grafted with hydrophilic (poly(ethylene glycol), mPEG) and/or hydrophobic groups (n-dodecyl) via a simple (one-pot) method and evaluate their physicochemical properties as a function of varying pH using rheology, small-angle Xray scattering (SAXS), dynamic light scattering (DLS) and zeta potential. The chitosan derivatives were prepared using reductive alkylation under mild reaction conditions and the chemical structure of the polymers was characterized by nuclear magnetic resonance (1H NMR) and CHN elemental analysis. Considering a constant mPEG/Chitosan molar ratio on modification of chitosan, the solubility of the polymer across a wide pH range (acidic, neutral and basic) could only be improved when some of the amino groups were submitted to reacetylation using the one-pot method. Under these conditions, solubility is maintained even with the simultaneous insertion of n-dodecyl. On the other hand, the solubility of derivatives obtained only through mPEG incorporation using the traditional methodology, or with the ndodecyl group, was similar to that of its precursor. The hydrophilic group promoted decreased viscosity of the polymer solutions at 10 g/L in acid medium. However, at basic pH, both viscosity and thermal stability increased, as well as exhibited a pronounced pseudoplastic behavior, suggesting strong intermolecular associations in the alkaline medium. The SAXS results showed a polyelectrolyte behavior with the decrease in pH for the polymer systems. DLS analyses revealed that although the dilute polymer solutions at 1 g/L and pH 3 exhibited a high density of protonated amino groups along the polymer chain, the high degree of charge contributed significantly to aggregation, promoting increased particle size with the decrease in pH. Furthermore, the hydrophobic group also contributed to increasing the size of aggregates in solution at pH 3, whereas the hydrophilic group helped reduce their size across the entire pH range. Nevertheless, the nature of aggregation was dependent on the pH of the medium. Zeta potential results indicated that its values do not depend solely on the surface charge of the particle, but are also dependent on the net charge of the medium. In this study, water soluble associative polymers exhibit properties that can be of great interest in the petroleum industry

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This work has the main objective to obtain nano and microcrystals of cellulose, extracted from the pineapple leaf fibres (PALF), as reinforcement for the manufacture of biocomposite films with polymeric matrices of Poly(vinyl alcohol) (PVA) and Poly(lactic acid) (PLA). The polymer matrices and the nano and microcrystals of cellulose were characterised by means of TGA, FTIR and DSC. The analysis was performed on the pineapple leaves to identify the macro and micronutrients. The fibers of the leaves of the pineapple were extracted in a desfibradeira mechanical. The PALF extracted were washed to remove washable impurities and subsequently treated with sodium hydroxide (NaOH) and sodium hypochlorite (NaClO) in the removal of impurities, such as fat, grease, pectates, pectin and lignin. The processed PALF fibers were hydrolysed in sulfuric acid (H2SO4) at a concentration of 13.5 %, to obtain nano and microcrystals of cellulose. In the manufacture of biocomposite films, concentrations of cellulose, 0 %, 1 %, 3 %, 6 %, 9% and 12% were used as reinforcement to the matrices of PVA and PLA. The PVA was dissolved in distilled water at 80 ± 5 oC and the PLA was dissolved in dichloromethane at room temperature. The manufacture of biocompósitos in the form of films was carried out by "casting". Tests were carried out to study the water absorption by the films and mechanical test of resistance to traction according to ASTM D638-10 with a velocity of 50 mm/min.. Chi-square statistical test was used to check for the existence of significant differences in the level of 0.05: the lengths of the PALF, lengths of the nano and microcrystals of cellulose and the procedures used for the filtration using filter syringe of 0.2 μm or filtration and centrifugation. The hydrophilicity of biocompósitos was analysed by measuring the contact angle and the thickness of biocompósitos were compared as well as the results of tests of traction. Statistical T test - Student was also applied with the significance level (0.05). In biodegradation, Sturm test of standard D5209 was used. Nano and microcrystals of cellulose with lengths ranging from 7.33 nm to 186.17 nm were found. The PVA films showed average thicknesses of 0.153 μm and PLA 0.210 μm. There is a strong linear correlation directly proportional between the traction of the films of PVA and the concentration of cellulose in the films (composite) (0,7336), while the thickness of the film was correlated in 0.1404. Nano and microcrystals of cellulose and thickness together, correlated to 0.8740. While the correlation between the cellulose content and tensile strength was weak and inversely proportional (- 0,0057) and thickness in -0.2602, totaling -0,2659 in PLA films. This can be attributed to the nano and microcrystals of cellulose not fully adsorbed to the PLA matrix. In the comparison of the results of the traction of the two polymer matrices, the nano and microcrystals have helped in reducing the traction of the films (composite) of PLA. There was still the degradation of the film of PVA, within a period of 20 days, which was not seen in the PLA film, on the other hand, the observations made in the literature, the average time to start the degradation is above 60 days. What can be said that the films are biodegradable composites, with hydrophilicity and the nano and microcrystals of cellulose, contribute positively in the improvement of the results of polymer matrices used.

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Considering the plant biodiversity in the Brazilian Northeast, whose components can be inserted into sustainable production systems, the jujube (Ziziphus joazeiro Mart.) emerges as to recovery of its fruit. The present study has as objective to characterize the fruit of the jujube under the physical, physicochemical and chemical approach and assess its conservation by spontaneous lactic fermentation under the influence of chloride, sodium, calcium and potassium. According to the legislation, vegetable acidified by fermentation that is subjected to lactic acid fermentation in order to achieve a final product pH less than or equal to 4.5. The results of the physical, chemical and physico-chemistry of ripe fruit jujube showed the potential of this species for agro-processing. The yield of edible portion (91.83%), soluble solids content (18,98º Brix), titratable acidity (0.14% citric acid), pH (5.30) and its composition, divided in moisture (79.01%), protein (2.01%), lipids (0.52%), carbohydrate (17.59%), fiber, ash (0.76%) and its minerals were consistent with the characteristic profile fruits, thus favoring the development of spontaneous lactic fermentation. The minimum pH and titratable acidity observed maximum in the fermentation process under the influence of mixtures of salts (NaCl and KCl NaCl2) values ranged from 3.4 to 3.7 and from 0.54 to 0.95 (% lactic acid), respectively. The profile of the lactic fermentation of fruit of jujube in brine, fermented microbiological quality and the result of analysis of primary sensory prepared preserved, the application of endorsed by the consumer sensory evaluation, more particularly, derived from fermented fruit preserved in the presence of chloride sodium, in accordance with the traditional techniques of lactic fermentation of vegetables. The results of sensory evaluation conducted with 100 consumers (tasters) revealed an acceptance rate equal to 78% of the preserve. Despite restrictions on the sensory acceptability of fermented under the influence of salts (KCl and CaCl2) substitutes sodium chloride, preserved these perspectives presented to balance the optimization of mixtures, health product safety and consumer awareness towards prefer a more healthy product with reduced sodium content.

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Synthesis of heterocyclic compounds, as quinoxaline derivatives, has being shown to be relevant and promissor due to expressive applications in biological and technological areas. This work was dedicated to the synthesis, characterization and reactivity of quinoxaline derivatives in order to obtain new chemosensors. (L)-Ascorbic acid (1) and 2,3-dichloro-6,7- dinitroquinoxalina (2) were explored as synthetic precursors. Starting from synthesis of 1 and characterization of compounds derived from (L)-ascorbic acid, studies were performed investigating the application of products as chemosensors, in which compound 36 demonstrated selective affinity for Cu2+ íons in methanolic solution, by naked-eye (colorimetric) and UVvisible analyses. Further, initial analysis suggests that 39 a Schiff’s base derived from 36 also presents this feature. Five quinoxaline derivatives were synthesized from building block 2 through nucleophilic aromatic substitution by aliphatic amines, in which controlling the experimental conditions allows to obtain both mono- and di-substituted derivatives. Reactivity studies were carried out with two purposes: i) investigate the possibility of 47 compound being a chemosensor for anion, based on its interaction with sodium hydroxide in DMSO, using image analysis and UV-visible spectroscopy; ii) characterize kinetically the conversion of compound 44 into 46 based on RGB and multivariate image analysis from TLC data, as a simple and inexpensive qualitative and quantitative tool.

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Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.

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Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.