Desenvolvimento de Sistemas Microparticulados Superparamagnéticos Gastro-resistentes para Diagnóstico e Terapêutica

This work aimed to develop a suitable magnetic system for administration by the oral route. In addition to that, it was intended to review the current uses of magnetic systems and the safety related to magnetic field exposure. Methods: Coprecipitation and emulsification/crosslinking were carried out in order to synthesize magnetite particles and to coat them, respectively. Results: According to literature review, it was found that magnetic particles present several properties such as magnetophoresis in magnetic field gradient, production of a surrounding magnetic field, and heat generation in alternated magnetic field. When the human organism is exposed to magnetic fields, several interaction mechanisms come into play. However, biological tissues present low magnetic susceptibility. As a result, the effects are not so remarkable. Concerning the development of a magnetic system for oral route, uncoated magnetite particles did undergo significant dissolution at gastric pH. On the other hand, such process was inhibited in the xylan-coated particles. Conclusions: Due to their different properties, magnetic systems have been widely used in biosciences. However, the consequent increased human exposure to magnetic fields has been considered relatively safe. Concerning the experimental work, it was developed a polymer-coated magnetic system. It may be very promising for administration by the oral route for therapy and diagnostic applications as dissolution at gastric pH hardly took place

Novos sistemas de liberação de fármacos à base de xilana

The aim of this work was to perform the extraction and characterization of xylan from corn cobs and prepare xylan-based microcapsules. For that purpose, an alkaline extraction of xylan was carried out followed by the polymer characterization regarding its technological properties, such as angle of repose, Hausner factor, density, compressibility and compactability. Also, a low-cost and rapid analytical procedure to identify xylan by means of infrared spectroscopy was studied. Xylan was characterized as a yellowish fine powder with low density and poor flow properties. After the extraction and characterization of the polymer, xylan-based microcapsules were prepared by means of interfacial crosslinking polymerization and their characterization was performed in order to obtain gastroresistant multiparticulate systems. This work involved the most suitable parameters of the preparation of microcapsules as well as the study of the process, scale-up methodology and biological analysis. Magnetic nanoparticles were used as a model system to be encapsulated by the xylan microcapsules. According to the results, xylan-based microcapsules were shown to be resistant to several conditions found along the gastrointestinal tract and they were able to avoid the early degradation of the magnetic nanoparticles

Aplicação de nanopartículas de quitosana com potencial de adjuvante na produção de soro contra o venneno do escorpião Tityus serrulatus

In Brazil, several species of scorpions are known to cause accidents which can lead to death, which are mainly belonging to the genus Tityus. The scorpion Tityus serrulatus is the main responsible for more severe cases. Anti-scorpion serums are routinely produced by various institutions, despite their effectiveness, quality and action depends on how quickly treatment is started. Studies have been developed in the search for appropriate technologies to encapsulate and release recombinant or natives proteins capable of inducing antibody production. In this context, chitosan copolymer which can be obtained from the partial deacetylation of chitin or in some microorganisms and it is biocompatible and biodegradable has been widely used for this purpose. This study aimed to search for a system release from chitosan nanoparticles for peptide / protein of the venom of the scorpion T. serrulatus, able to provide a new model of immunization in animals, in order to obtain a potential novel polyclonal serum, anti-venom T. serrulatus. The chitosan nanoparticles were prepared by ionic gelation with polyanion tripolyphosphate (TPP). After standardizing the concentrations of TPP and chitosan was evaluated the efficiency of incorporation of bovine serum albumin (BSA) and scorpion venom, showed particle size compatible with the intended purpose. The particles showed adequate size around 200nm. The crosslinking was confirmed by absorption spectroscopy in the infrared. After verified the high encapsulation efficiency (EE) for acid bicinconínico method (BCA) protein assay and the particle size distribution, the success of the technique was proven and the potential for in vivo application of nanoparticles. The experimental animals were vaccinated and the antibodies measured by ELISA

Síntese e caracterização de látices acrílicos reticulados com (1,6-diacrilato propoxilato hexanodiol) via polimerização em emulsão

Latices based on acrylic acid and ethyl methacrylate, crosslinked with 1,6‐propoxylate‐hexanodiol diacrylate were synthesized via emulsion polymerization with different monomeric compositions. The resultant latices were thickened with different NaOH/(acrylic acid) molar ratios and were characterized by titrimetry, zeta potential measurements, turbidimetry, and capillary viscometry. Intrinsic viscosity was determined for an uncrosslinked copolymer, using toluene as solvent. All the latices were coagulated with NaCl and washed with water at 60°C analyzed by FTIR spectrophotometry, in order to characterize functional groups from the copolymer and crosslinking agent.

Caracterização do processo de gelificação de soluções quitosana utilizando reometria e espalhamento dinâmico da luz

Gels consist of soft materials with vast use in several activities, such as in pharmaceutical industry, food science, and coatings/textile applications. In order to obtain these materials, the process of gelification, that can be physical (based on physical interactions) and/or chemical (based on covalent crosslinking), has to be carried out. In this work we used dynamic light scattering (DLS) and rheometry to monitor the covalent gelification of chitosan solutions by glutaraldehyde. Intensity correlation function (ICF) data was obtained from DLS and the exponential stretched Kohrausch-William-Watts function (KWW) was fitted to them. The parameters of the KWW equation, β, Γ and C were evaluated. These methods were effective in clarifying the process of sol-gel transition, with the emergence of non-ergodicity, and determining the range of gelation observed in about 10-20 minutes. The dependence between apparent viscosity on reaction time was used to support the discussion proposed.

Obtenção e caracterização de nanopartículas de quitosana

Chitosan nanoparticles have been used in several systems for the controlled release of drugs. The aim of this study was to obtain and characterize chitosan nanoparticles prepared by the method of coacervation / precipitation using sodium sulfate at different concentrations as the crosslinking agent. The characterization was done using zeta potential and small angle Xray scattering, SAXS. The dispersions of chitosan were obtained at pH 1 and pH = 3. The results of zeta potential at pH = 1 ranged from +64.8 to +29.27 mV and for pH = 3 they varied from +72.4 to +23.48 mV, indicating that the chain of chitosan is positively charged in acidic pH and the behavior of nanoparticles in terms of surface charge was independent of pH. However, the results indicated a dependence of particle size in relation to pH. This difference in behavior was explained by the influence of enthalpic and entropic components

Partículas inteligentes de poli (nisopropilacrilamida), quitosana e poli (ácido acrílico): efeito da temperatura e do pH sobre suas propriedades em suspensões aquosas

The present study describes the stability and rheological behavior of suspensions of poly (N-isopropylacrylamide) (PNIPAM), poly (N-isopropylacrylamide)-chitosan (PNIPAMCS), and poly (N-isopropylacrylamide)-chitosan-poly (acrylic acid) (PNIPAM-CS-PAA) crosslinked particles sensitive to pH and temperature. These dual-sensitive materials were simply obtained by one-pot method, via free-radical precipitation copolymerization with potassium persulfate, using N,N -methylenebisacrylamide (MBA) as a crosslinking agent. Incorporation of the precursor materials into the chemical networks was confirmed by elementary analysis and infrared spectroscopy. The influence of external stimuli such as pH and temperature, or both, on particle behavior was investigated through rheological measurements, visual stability tests and analytical centrifugation. The PNIPAM-CS particles showed higher stability in acid and neutral media, whereas PNIPAM-CS-PAA particles were more stable in neutral and alkaline media, both below and above the LCST of poly (Nisopropylacrylamide) (stability data). This is due to different interparticle interactions, as well as those between the particles and the medium (also evidenced by rheological data), which were also influenced by the pH and temperature of the medium. Based on the results obtained, we found that the introduction of pH-sensitive polymers to crosslinked poly (Nisopropylacrylamide) particles not only produced dual-sensitive materials, but allowed particle stability to be adjusted, making phase separation faster or slower, depending on the desired application. Thus, it is possible to adapt the material to different media

Obtenção de dispersões de complexos polieletrolíticos à base de quitosana e poli(ácido metacrílico) e análise de adsorção de albumina bovina sérica

Dispersions composed of polyelectrolyte complexes based on chitosan and poly(methacrylic acid), PMAA, were obtained by the dropping method and template polymerization. The effect of molecular weight of PMAA and ionic strength on the formation of chitosan/poly(methacrylic acid), CS/PMAA, complexes was evaluated using the dropping method. The increase in molecular weight of PMAA inhibited the formation of insoluble complexes, while the increase in ionic strength first favored the formation of the complex followed by inhibiting it at higher concentrations. The polyelectrolyte complexation was strongly dependent on macromolecular dimensions, both in terms of molecular weight and of coil expansion/contraction driven by polyelectrolyte effect. The resultant particles from dropping method and template polymerization were characterized as having regions with different charge densities: chitosan predominating in the core and poly(methacrylic acid) at the surface, the particles being negatively charged, as a consequence. Albumin was adsorbed on templatepolymerized CS/PMAA complexes (after crosslinking with glutardialdehyde) and pH was controlled in order to obtain two conditions: (i) adsorption of positively charged albumin, and (ii) adsorption of albumin at its isoelectric point. Adsorption isotherms and zeta potential measurements showed that albumin adsorption was controlled by hydrogen bonding/van der Waals interactions and that brushlike structures may enhance adsorption of albumin on these particles

Aplicação de géis de goma guar no processo de clarificação de salmouras e águas produzidas

Produced water is considered the main effluent of the oil industry, due to their increased volume in mature fields and its varied composition. The oil and grease content (TOG) is the main parameter for the final disposal of produced water. In this context, it is of great significance to develop an alternative method based on guar gum gel for the treatment of synthetic produced water, and using as the differential a polymer having high hydrophilicity for clarifying waters contaminated with oil. Thus, this study aims to evaluate the efficiency of guar gum gels in the remotion of oil from produced water. Guar gum is a natural polymer that, under specific conditions, forms three-dimensional structures, with important physical and chemical properties. By crosslinking the polymer chains by borate ions in the presence of salts, the effect salting out occurs, reducing the solubility of the polymer gel in water. As a result, there is phase separation with the oil trapped in the collapsed gel. The TOG was quantified from the spectroscopy in the ultraviolet and visible region. The system was proven to be highly efficient in the removal of dispersed oil from water produced synthetically, reaching removal percentages above 90%.

Micropartículas contendo nanopartículas de quitosana usando sulfato e genipina para liberação modificada da triancinolona: obtenção, caracterização e estudo em células tumorais

Chitosan is a polymer biocompatibility and biodegradability widely used in drug delivery systems. The co-crosslinking of chitosan with sodium sulfate and genipin, to form particulate systems is related of making them more resistant to acidic pH and to modulate the release kinetics for the oral route. Triamcinolone is a glucocorticoid with anti-inflammatory and immunosuppressive actions. The nanoparticles were prepared by co-crosslinking and characterized for particle size, PDI, zeta potential, crosslinking degree, encapsulation rate, morphology, infrared spectroscopy, thermal analysis, release kinetics and cells studies. The nanoparticles were prepared initially without genipin with sodium sulphate and the particles parameters were monitored in function of different ratio of drug / polymer, different concentrations of sodium sulfate and polysorbate 80 and the drip mode of crosslinkers on polymers. After optimizing conditions, the chosen system parameters without genipin included mean diameter of 312.20 ± 5.70 nm, PDI 0.342 ± 0.013 and zeta potential of 20.18 ± 2.28 mV. The genipin was introduced into the system analyzing different concentrations (0.5, 1.0 and 2.0 mM) and crosslinking times (3, 6, 12 and 24 h). Evaluating crosslinking time with genipin (0.5 mM) it was showed that varying the genipin reaction time the systems size ranged from 235.1 to 334.4 nm, the PDI from 0.321 to 0.392 and zeta potential 20.92 to 30.39 mV. The crosslinking degree that coud vary from 14 to 30 %. Nanoparticles without genipina, 6 h and 24 h crosslinking time were dried by spray-drying method. Analysis by scanning electron micrograph (SEM) revealed that the microparticles showed spherical morphology. The encapsulation rate was 75 ± 2.3 % using validated HPLC methodology. The infrared analysis showed chemical interactions between the components of the formulation. Thermal analysis showed that systems with a higher degree of crosslinking had a higher thermal stability. On release kinetics, increasing the degree of crosslinking was able to decrease the concentration and rate of release of triamcinolone. In studies with liver cancer cells (HepG2) and colon (HT-29), the microparticulate prepared with triamcinolone and 24 h of crosslinking with genipin showed a potential for antitumor activity in hepatic cell line HepG2. Therefore, a new delivery system for triamcinolone on polymeric nanoparticles of chitosan cocrosslinked with genipin and sodium sulfate was obtained with hepatic antitumor potential.

Obtenção e caracterização de sistemas particulados de quitosana para liberação gástrica de amoxicilina

The infection caused by Helicobacter pylori (H. pylori) is associated with gastroduodenal inflammation can lead to the development of gastritis, gastric or duodenal ulcer and gastric cancer (type 1 carcinogen for stomach cancer). Amoxicillin is used as first-line therapy in the treatment of H. pylori associated to metronidazole or clarithromycin, and a proton pump inhibitor. However, the scheme is not fully effective due to inadequate accumulation of antibiotics in gastric tissue, inadequate efficacy of ecological niche of H. pylori, and other factors. In this context, this study aimed to obtaining and characterization of particulate systems gastrorretentivos chitosan - amoxicillin aiming its use for treatment of H. pylori infections. The particles were obtained by the coacervation method / precipitation using sodium sulfate as precipitating agent and crosslinking and two techniques: addition of amoxicillin during preparation in a single step and the sorption particles prior to amoxycillin prepared by coacervation / precipitation and spray drying. The physicochemical characterization of the particles was performed by SEM, FTIR, DSC, TG and XRD. The in vitro release profile of amoxycillin free and incorporated in the particles was obtained in 0.1 N HCl (pH = 1.2). The particles have higher encapsulation efficiency to 80% spherical shape with interconnected particles or adhered to each other, the nanometric diameter to the systems obtained by coacervation / precipitation and fine for the particles obtained by spray drying. The characterization by FTIR, DSC and XRD showed that the drug was incorporated into the nanoparticles dispersed in the polymeric matrix. Thermal analysis (TG and DSC) indicated that encapsulation provides greater heat stability to the drug. Amoxicillin encapsulated in nanoparticles had slower release compared to free drug. The particles showed release profile with a faster initial stage (burst effect) reaching a maximum at 30 minutes 35% of amoxicillin for the system in 1: 1 ratio relative to the polymer and 80% for the system in the ratio 2: 1. Although simple and provide high encapsulation efficiency of amoxicillin, the process of coacervation, precipitation in one step using sodium sulfate as precipitant / cross-linker must be optimized in order to adjust the release kinetics according to the intended application.

Usos de membranas de quitosana na remoção de cobre em águas residuais

In this work a chitosan (CS) ionically crosslinked were manufactured by treatment with sulfuric acid solution for application in the treatment of wastewater from oil industry. Two crosslinking process were developed: homogeneous and heterogeneous. In the homogeneous process the ratio molar of SO42-/ NH3+ (1:6 and 1:4) were the variable analyzed, denominated CS16 and CS14 respectively. In the heterogeneous process the soaking time of the membranes in sulfuric acid solution were the variable studied, being used times of 5 (CS5) and 30 (CS30) minutes. FTIR-ATR results indicated no changes in the characteristics of chitosan after homogeneous crosslinking process, while heterogeneous crosslinking showed formation of ionic bonds between protonated groups from chitosan and the crosslinking agent sulfate ions. TG/DTG and XRD analysis confirmed the formation of these interactions, as also shown the new structure on the surface region of CS5 and CS30 membranes compared to CS, CS16 e CS14. Swelling test in aqueous medium have shown that crosslinking process reduced the membrane sorption capacity. Swelling test in acid medium demonstrated that CS16 and CS14 membranes increasing the adsorption capacity up to a maximum percentage of 140% approximately, whereas the CS5 e CS30 reached a maximum of 60%. The mechanical properties indicated the stiff and ductile behavior of crosslinked membrane. Adsorption experiments of CuCl2 results that CS16 membranes reached the efficiency maximum with 73% of copper removal at pH 5.0 and 87% at pH 4.0. The experiments with CuSO4 also obtained efficiency maximum to the CS16 membrane and 80% to the removal of Cu2+ ions. Also was verified that the increase of concentration and temperature cause a decrease in the adsorption capacity for all membranes. Kinetics study indicated that pseudo-second-order obtained characterized better the membranes. Equilibrium studies demonstrated that the CS, CS16 and CS14 follow the Langmuir model, whereas CS5 and CS30 follows Freundlich model. Filtration experiments results with rejection maximum to the CS16 and CS5 membranes, reaching 92 and 98% respectively.

Usos de membranas de quitosana na remoção de cobre em águas residuais

In this work a chitosan (CS) ionically crosslinked were manufactured by treatment with sulfuric acid solution for application in the treatment of wastewater from oil industry. Two crosslinking process were developed: homogeneous and heterogeneous. In the homogeneous process the ratio molar of SO42-/ NH3+ (1:6 and 1:4) were the variable analyzed, denominated CS16 and CS14 respectively. In the heterogeneous process the soaking time of the membranes in sulfuric acid solution were the variable studied, being used times of 5 (CS5) and 30 (CS30) minutes. FTIR-ATR results indicated no changes in the characteristics of chitosan after homogeneous crosslinking process, while heterogeneous crosslinking showed formation of ionic bonds between protonated groups from chitosan and the crosslinking agent sulfate ions. TG/DTG and XRD analysis confirmed the formation of these interactions, as also shown the new structure on the surface region of CS5 and CS30 membranes compared to CS, CS16 e CS14. Swelling test in aqueous medium have shown that crosslinking process reduced the membrane sorption capacity. Swelling test in acid medium demonstrated that CS16 and CS14 membranes increasing the adsorption capacity up to a maximum percentage of 140% approximately, whereas the CS5 e CS30 reached a maximum of 60%. The mechanical properties indicated the stiff and ductile behavior of crosslinked membrane. Adsorption experiments of CuCl2 results that CS16 membranes reached the efficiency maximum with 73% of copper removal at pH 5.0 and 87% at pH 4.0. The experiments with CuSO4 also obtained efficiency maximum to the CS16 membrane and 80% to the removal of Cu2+ ions. Also was verified that the increase of concentration and temperature cause a decrease in the adsorption capacity for all membranes. Kinetics study indicated that pseudo-second-order obtained characterized better the membranes. Equilibrium studies demonstrated that the CS, CS16 and CS14 follow the Langmuir model, whereas CS5 and CS30 follows Freundlich model. Filtration experiments results with rejection maximum to the CS16 and CS5 membranes, reaching 92 and 98% respectively.