RESUMO
Thin composite films comprising two primary representatives of conducting polymers, poly(3, 4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPy), with eco-friendly cellulose nanocrystals (CNC) were prepared through electrochemical polymerization. The combination of CNC and PEDOT (or PPy) results in the formation of films with highly different surface topography and thickness. Intriguingly, different surface conductivity of PEDOT and PPy was revealed by atomic force microscopy albeit that the electrochemical properties were rather similar. The biological properties of the composites in contact with prospective human induced pluripotent stem cells (hiPSC) and cardiomyocytes derived from hiPSC demonstrated good cytocompatibility of both composites and their potential in engineering of electro-sensitive tissues. The as-prepared conducting, eco-friendly and cytocompatible composites are thus promising candidates for biomedical applications where stimuli-responsivity is a crucial cell-instructive property.
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Células-Tronco Pluripotentes Induzidas , Nanopartículas , Humanos , Polímeros/química , Celulose/química , Engenharia Tecidual , Estudos Prospectivos , Pirróis/químicaRESUMO
The in situ coating of polymer substrate with polypyrrole, described herein with detailed know-how, represents a novel technique of surface functionalization. The choice of oxidizing agent and the polymerization time both affect the properties of the thin polypyrrole layer. The specific conductivity, free surface energy, thickness, topography, and FTIR spectra of polypyrrole layer were determined. The conductive coatings were further used to functionalize both isotropic and anisotropic electrospun polyurethane nanofibrous mats to show their applicability and study the bioactive effect of both the anisotropy and conductivity together. The morphology of composites was studied by means of atomic force microscopy and scanning electron microscopy. A complex cytocompatibility study was performed, including determining cytotoxicity by optical and fluorescence microscopy, the advanced qualification of cell morphology by cell-image analysis, and a study of stem cell behavior. The results clearly showed the significant impact of substrate modification on cells, especially on fibroblasts while the embryonic stem cells were less affected. This study shows not only the effective way to prepare a thin conducting layer based on polypyrrole but also demonstrates its importance for the fabrication of smart biomaterials.
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In this work, conductive composite hydrogels with covalently attached polypyrrole (PPy) nanoparticles are prepared. Hydrogels are based on partially re-acetylated chitosan soluble at physiological pH without any artificial structural modifications or need for an acidic environment, which simplifies synthesis and purification. Low-toxic and sustainable dialdehyde cellulose (DAC) was used for crosslinking chitosan and covalent anchoring of PPy colloidal particles. The condensation reaction between DAC and PPy is reported for the first time and improves not only the anchoring of PPy particles but also control over the properties of the final composite. The soluble chitosan and PPy particles are shown to act in synergy, which improves the biological properties of the materials. Prepared composite hydrogels are non-cytotoxic, non-irritating, antibacterial, can capture reactive oxygen species often related to excessive inflammation, have conductivity similar to human tissues, enhance in vitro cell growth (migration assay), and have immunomodulatory effects related to the stimulation of neutrophils and macrophages. The covalent attachment of PPy also strengthens the hydrogel network. The aldol condensation as a method for PPy covalent anchoring thus presents an interesting possibility for the development of advanced biomaterials in the future.
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Quitosana , Humanos , Quitosana/química , Polímeros/química , Hidrogéis/farmacologia , Hidrogéis/química , Pirróis/química , Antioxidantes/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Inflamatórios/farmacologiaRESUMO
A green, nature-friendly synthesis of polyaniline colloidal particles based on enzyme-assisted oxidation of aniline with horseradish peroxidase and chitosan or poly(vinyl alcohol) as steric stabilizers was successfully employed. Physicochemical characterization revealed formation of particles containing the polyaniline emeraldine salt and demonstrated only a minor effect of polymer stabilizers on particle morphology. All tested colloidal particles showed in vitro antioxidation activity determined via scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. In vitro, they were able to reduce oxidative stress and inhibit the production of reactive oxygen species by neutrophils and inflammatory cytokines by macrophages. The anti-inflammatory effect observed was related to their antioxidant activity, especially in the case of neutrophils. The particles can thus be especially advantageous as active components of biomaterials modulating the early stages of inflammation. In addition to the immunomodulatory effect, the presence of intrinsically conducting polyaniline can impart cell-instructive properties to the particles. The approach to particle synthesis that we employedâan original one using environmentally friendly and biocompatible horseradish peroxidaseârepresents a smart way of preparing conducting particles with unique properties, which can be further modified by the stabilizers used.
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Compostos de Anilina , Antioxidantes , Compostos de Anilina/química , Antioxidantes/farmacologia , Catálise , Peroxidase do Rábano Silvestre , PolimerizaçãoRESUMO
Bio-inspired conductive scaffolds composed of sodium hyaluronate containing a colloidal dispersion of water-miscible polyaniline or polypyrrole particles (concentrations of 0.108, 0.054 and 0.036% w/w) were manufactured. For this purpose, either crosslinking with N-(3-dimethylaminopropyl-N-ethylcarbodiimide hydrochloride and N-hydroxysuccinimid or a freeze-thawing process in the presence of poly(vinylalcohol) was used. The scaffolds comprised interconnected pores with prevailing porosity values of ~ 30% and pore sizes enabling the accommodation of cells. A swelling capacity of 92-97% without any sign of disintegration was typical for all samples. The elasticity modulus depended on the composition of the scaffolds, with the highest value of ~ 50 kPa obtained for the sample containing the highest content of polypyrrole particles. The scaffolds did not possess cytotoxicity and allowed cell adhesion and growth on the surface. Using the in vivo-mimicking conditions in a bioreactor, cells were also able to grow into the structure of the scaffolds. The technique of scaffold preparation used here thus overcomes the limitations of conductive polymers (e.g. poor solubility in an aqueous environment, and limited miscibility with other hydrophilic polymer matrices) and moreover leads to the preparation of cytocompatible scaffolds with potentially cell-instructive properties, which may be of advantage in the healing of damaged electro-sensitive tissues.
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Polímeros , Engenharia Tecidual , Materiais Biocompatíveis/química , Ácido Hialurônico , Polímeros/química , Porosidade , Pirróis/química , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
An innovative multi-step phase separation process was used to prepare tissue culture for the polystyrene-based, hierarchically structured substrates, which mimicked in vivo microenvironment and architecture. Macro- (pore area from 3000 to 18,000 µm2; roughness (Ra) 7.2 ± 0.1 µm) and meso- (pore area from 50 to 300 µm2; Ra 1.1 ± 0.1 µm) structured substrates covered with micro-pores (area around 3 µm2) were prepared and characterised. Both types of substrate were suitable for human-induced pluripotent stem cell (hiPSC) cultivation and were found to be beneficial for the induction of cardiomyogenesis in hiPSC. This was confirmed both by the number of promoted proliferated cells and the expressions of specific markers (Nkx2.5, MYH6, MYL2, and MYL7). Moreover, the substrates amplified the fluorescence signal when Ca2+ flow was monitored. This property, together with cytocompatibility, make this material especially suitable for in vitro studies of cell/material interactions within tissue-mimicking environments.
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Materiais Biocompatíveis/química , Diferenciação Celular , Fluorescência , Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Poliestirenos/química , Proliferação de Células , HumanosRESUMO
The growing application of materials containing TiO2 particles has led to an increased risk of human exposure, while a gap in knowledge about the possible adverse effects of TiO2 still exists. In this work, TiO2 particles of rutile, anatase, and their commercial mixture were exposed to various environments, including simulated gastric fluids and human blood plasma (both representing in vivo conditions), and media used in in vitro experiments. Simulated body fluids of different compositions, ionic strengths, and pH were used, and the impact of the absence or presence of chosen enzymes was investigated. The physicochemical properties and agglomeration of TiO2 in these media were determined. The time dependent agglomeration of TiO2 related to the type of TiO2, and mainly to the type and composition of the environment that was observed. The presence of enzymes either prevented or promoted TiO2 agglomeration. TiO2 was also observed to exhibit concentration-dependent cytotoxicity. This knowledge about TiO2 behavior in all the abovementioned environments is critical when TiO2 safety is considered, especially with respect to the significant impact of the presence of proteins and size-related cytotoxicity.
Assuntos
Nanopartículas Metálicas/química , Plasma/metabolismo , Titânio/química , Titânio/metabolismo , Animais , Doadores de Sangue , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cristalização , Meios de Cultura/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/efeitos adversos , Camundongos , Concentração Osmolar , Tamanho da Partícula , Saliva/metabolismo , Propriedades de Superfície , Titânio/efeitos adversos , Água/metabolismoRESUMO
HYPOTHESIS: In the preparation of oleogels based on Pickering-emulsions, the choice of the preparation route is critical to withstand drying under ambient conditions, as it conditions the composition of the interfacial layer at the oil-water interface. EXPERIMENTS: Hexadecane and olive oil oleogels were prepared using an emulsion-template approach from oil-in-water emulsions formulated with cellulose nanocrystals (CNC) and sodium caseinate (CAS) added in different orders (CNC/CAS together; first CAS then CNC; first CNC then CAS). The oleogels were formed from preconcentrated emulsions by drying at ambient temperature. The structure of the gels was characterised by confocal laser scanning microscopy, and the gels were assessed in terms of viscoelastic properties and redispersibility. FINDINGS: The properties of oleogels were controlled by 1) the composition of the surface layer at oil-water interface; 2) the amount and type of non-adsorbed stabilizer; and 3) the composition and viscosity of oils (hexadecane vs. olive oil). For the oleogels prepared from starting emulsions stabilized with CNC with subsequent addition of CAS, and free CAS present in aqueous phase, the elastic component was prevalent. Overall, the dominating species at the oil-water interface controlled the emulsion behaviour and stability, as well as viscoelastic behaviour of the resulting oleogels and their redispersibility.
RESUMO
Tracer diffusion coefficients obtained from the Taylor dispersion technique at 25.0 °C were measured to study the influence of sodium, ammonium and magnesium salts at 0.01 and 0.1 mol dm-3 on the transport behavior of sodium hyaluronate (NaHy, 0.1%). The selection of these salts was based on their position in Hofmeister series, which describe the specific influence of different ions (cations and anions) on some physicochemical properties of a system that can be interpreted as a salting-in or salting-out effect. In our case, in general, an increase in the ionic strength (i.e., concentrations at 0.01 mol dm-3) led to a significant decrease in the limiting diffusion coefficient of the NaHy 0.1%, indicating, in those circumstances, the presence of salting-in effects. However, the opposite effect (salting-out) was verified with the increase in concentration of some salts, mainly for NH4SCN at 0.1 mol dm-3. In this particular salt, the cation is weakly hydrated and, consequently, its presence does not favor interactions between NaHy and water molecules, promoting, in those circumstances, less resistance to the movement of NaHy and thus to the increase of its diffusion (19%). These data, complemented by viscosity measurements, permit us to have a better understanding about the effect of these salts on the transport behaviour of NaHy.
Assuntos
Ânions/química , Cátions/química , Ácido Hialurônico/química , Água/química , Sulfato de Amônio/química , Transporte Biológico , Difusão , Cloreto de Lítio/química , Sulfato de Magnésio/química , Concentração Osmolar , Sais/química , Cloreto de Sódio/química , Soluções , Sulfatos/química , Temperatura , Tiocianatos/química , ViscosidadeRESUMO
The active role of biomaterials in the regeneration of tissues and their ability to modulate the behavior of stem cells in terms of their differentiation is highly advantageous. Here, polypyrrole, as a representantive of electro-conducting materials, is found to modulate the behavior of embryonic stem cells. Concretely, the aqueous extracts of polypyrrole induce neurogenesis within embryonic bodies formed from embryonic stem cells. This finding ledto an effort to determine the physiological cascade which is responsible for this effect. The polypyrrole modulates signaling pathways of Akt and ERK kinase through their phosphorylation. These effects are related to the presence of low-molecular-weight compounds present in aqueous polypyrrole extracts, determined by mass spectroscopy. The results show that consequences related to the modulation of stem cell differentiation must also be taken into account when polypyrrole is considered as a biomaterial.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Corpos Embrioides/efeitos dos fármacos , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Polímeros/farmacologia , Pirróis/farmacologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular/genética , Linhagem Celular , Corpos Embrioides/citologia , Expressão Gênica/efeitos dos fármacos , Camundongos , Estrutura Molecular , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Fator de Transcrição PAX6/genética , Polímeros/química , Pirróis/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição SOXB1/genéticaRESUMO
Novel composite films combining biocompatible polysaccharides with conducting polyaniline (PANI) were prepared via the in-situ polymerization of aniline hydrochloride in the presence of sodium hyaluronate (SH) or chitosan (CH). The composite films possess very good cytocompatibility in terms of adhesion and proliferation of two lines of human induced pluripotent stem cells (hiPSC). Moreover, the cardiomyogenesis and even formation of beating clusters were successfully induced on the films. The proportion of formed cardiomyocytes demonstrated excellent properties of composites for tissue engineering of stimuli-responsive tissues. The testing also demonstrated antibacterial activity of the films against E. coli and PANI-SH was able to reduce bacterial growth from 2 × 105 to < 1 cfu cm-2. Physicochemical characterization revealed that the presence of polysaccharides did not notably influence conductivities of the composites being â¼1 and â¼2 S cm-1 for PANI-SH and PANI-CH respectively; however, in comparison with neat PANI, it modified their topography making the films smoother with mean surface roughness of 4 (PANI-SH) and 14 nm (PANI-CH). The combination of conductivity, antibacterial activity and mainly cytocompatibility with hiPSC opens wide application potential of these polysaccharide-based composites.
Assuntos
Antibacterianos/química , Materiais Biocompatíveis/química , Quitosana/química , Ácido Hialurônico/química , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Nanocompostos/química , Compostos de Anilina/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Condutividade Elétrica , Escherichia coli/efeitos dos fármacos , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Polimerização , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície , Engenharia Tecidual/métodosRESUMO
Conducting polymers (CP) can be used as pH- and/or electro-responsive components in various bioapplications, for example, in 4D smart scaffolds. The ability of CP to maintain conductivity under physiological conditions is, therefore, their crucial property. Unfortunately, the conductivity of the CP rapidly decreases in physiological environment, as their conducting salts convert to non-conducting bases. One of the promising solutions how to cope with this shortcoming is the use of alternative "doping" process that is not based on the protonation of CP with acids but on interactions relying in acidic hydrogen bonding. Therefore, the phosphonates (dimethyl phosphonate, diethyl phosphonate, dibutyl phosphonate, or diphenyl phosphonate) were used to re-dope two most common representatives of CP, polyaniline (PANI) and polypyrrole (PPy) bases. As a result, PANI doped with organic phosphonates proved to have significantly better stability of conductivity under different pH. It has also been shown that cytotoxicity of studied materials determined on embryonic stem cells and their embryotoxicity, determined as the impact on cardiomyogenesis and erythropoiesis, depend both on the polymer and phosphonate types used. With the exception of PANI doped with dibutyl phosphonate, all PPy-based phosphonates showed better biocompatibility than the phosphonates based on PANI.
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Compostos de Anilina/química , Materiais Biocompatíveis/química , Organofosfonatos/química , Polímeros/química , Pirróis/química , Compostos de Anilina/farmacologia , Animais , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Condutividade Elétrica , Concentração de Íons de Hidrogênio , Camundongos , Células-Tronco Embrionárias Murinas , Polímeros/farmacologia , Pirróis/farmacologiaRESUMO
Caseinate-stabilized emulsions of black cumin (Nigella sativa) and tamanu (Calophyllum inophyllum) oils were studied in terms of preparation, characterization, and antibacterial properties. The oils were described while using their basic characteristics, including fatty acid composition and scavenging activity. The oil-in-water (o/w) emulsions containing the studied oils were formulated, and the influence of protein stabilizer (sodium caseinate (CAS), 1-12 wt%), oil contents (5-30 wt%), and emulsification methods (high-shear homogenization vs sonication) on the emulsion properties were investigated. It was observed that, under both preparation methods, emulsions of small, initial droplet sizes were predominantly formed with CAS content that was higher than 7.5 wt%. Sonication was a more efficient emulsification procedure and was afforded emulsions with smaller droplet size throughout the entire used concentration ranges of oils and CAS when compared to high-shear homogenization. At native pH of ~ 6.5, all of the emulsions exhibited negative zeta potential that originated from the presence of caseinate. The antibacterial activities of both oils and their emulsions were investigated with respect to the growth suppression of common spoilage bacteria while using the disk diffusion method. The oils and selected emulsions were proven to act against gram positive strains, mainly against Staphylococcus aureus (S. aureus) and Bacillus cereus (B. cereus); regrettably, the gram negative species were fully resistant against their action.
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Hemocompatibility is an essential prerequisite for the application of materials in the field of biomedicine and biosensing. In addition, mixed ionic and electronic conductivity of conducting polymers is an advantageous property for these applications. Heparin-like materials containing sulfate, sulfamic, and carboxylic groups may have an anticoagulation effect. Therefore, sodium dodecylbenzenesulfonate, 2-aminoethane-1-sulfonic acid and N-(2-acetamido)-2-aminoethanesulfonic acid were used for modification of the representative of conducting polymers, polyaniline, and the resulting products were studied in the context of interactions with human blood. The anticoagulation activity was then correlated to surface energy and conductivity of the materials. Results show that anticoagulation activity is highly affected by the presence of suitable functional groups originating from the used heparin-like substances, and by the properties of polyaniline polymer itself.
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A new hyaluronan derivative modified with ß-cyclodextrin units (CD-HA) was prepared via the click reaction between propargylated hyaluronan and monoazido-cyclodextrin (CD) to achieve a degree of substitution of 4%. The modified hyaluronan was characterized by 1H-nuclear magnetic resonance spectroscopy (NMR) and size exclusion chromatography. Subsequent 1H-NMR and isothermal calorimetric titration experiments revealed that the CD units on CD-HA can form virtual 1:1, 1:2, and 1:3 complexes with one-, two-, and three-site adamantane-based guests, respectively. These results imply that the CD-HA chains used the multitopic guests to form a supramolecular cross-linked network. The free CD-HA polymer was readily restored by the addition of a competing macrocycle, which entrapped the cross-linking guests. Thus, we demonstrated that the new CD-HA polymer is a promising component for the construction of chemical stimuli-responsive supramolecular architectures.
Assuntos
Ácido Hialurônico/química , Estrutura Molecular , Polímeros/química , beta-Ciclodextrinas/química , Calorimetria , Química Click , Ácido Hialurônico/síntese química , Espectroscopia de Ressonância Magnética , Polímeros/síntese química , beta-Ciclodextrinas/síntese químicaRESUMO
HYPOTHESIS: The interactions between two bio-based emulsifiers, namely cellulose nanocrystals (CNC) and the surface active sodium caseinate (CAS), can influence the formation and stability of oil-in-water emulsion (O/W). EXPERIMENTS: After studying the interactions between CNC and CAS, in bulk, and at air-water and liquid-liquid interfaces, emulsions have been prepared through different routes of addition, at pH 7 and 3, at which CNC and CAS had repulsive and attractive interactions, respectively. The routes of addition were (1) CAS and CNC simultaneously, (2) CAS first followed by CNC in a subsequent emulsification step and (3) CNC first, followed by CAS. The emulsions were characterized by laser diffraction and optical microscopy. FINDINGS: At pH 7, in the case of repulsive interactions, the surface activity of CAS was balanced by the irreversible adsorption of CNC, irrespectively of the route of emulsification. At pH 3, in the case of attractive interactions, using route (1), the aggregates CAS-CNC provided better emulsification than CNC and CAS alone. For emulsions prepared by route (2) and (3), gelling was observed which could be controlled through the order of addition. Emulsions prepared at pH 7 then adjusted to pH 3 exhibited an increase in viscosity, while the droplet size was not affected.
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Caseínas/química , Celulose/química , Emulsificantes/química , Emulsões/química , Nanopartículas/química , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Propriedades de Superfície , ViscosidadeRESUMO
The cytocompatibility of cardiomyocytes derived from embryonic stem cells and neural progenitors, which were seeded on the surface of composite films made of graphene oxide (GO) and polypyrrole (PPy-GO) or poly(3,4-ethylenedioxythiophene) (PEDOT-GO) are reported. The GO incorporated in the composite matrix contributes to the patterning of the composite surface, while the electrically conducting PPy and PEDOT serve as ion-to-electron transducers facilitating electrical stimulation/sensing. The films were fabricated by a simple one-step electropolymerization procedure on electrically conducting indium tin oxide (ITO) and graphene paper (GP) substrates. Factors affecting the cell behaviour, i.e. the surface topography, wettability, and electrical surface conductivity, were studied. The PPy-GO and PEDOT-GO prepared on ITO exhibited high surface conductivity, especially in the case of the ITO/PPy-GO composite. We found that for cardiomyocytes, the PPy-GO and PEDOT-GO composites counteracted the negative effect of the GP substrate that inhibited their growth. Both the PPy-GO and PEDOT-GO composites prepared on ITO and GP significantly decreased the cytocompatibility of neural progenitors. The presented results enhance the knowledge about the biological properties of electroactive materials, which are critical for tissue engineering, especially in context stimuli-responsive scaffolds.
Assuntos
Condutividade Elétrica , Eletroquímica , Grafite/farmacologia , Miócitos Cardíacos/citologia , Células-Tronco Neurais/citologia , Polímeros/farmacologia , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Polímeros/química , Pirróis/química , Água/químicaRESUMO
Colloidal polyaniline dispersions stabilized with biocompatible polysaccharides, sodium hyaluronate and chitosan (both with two different molecular weights), were successfully formulated. The colloids were characterized by UV-vis spectra, particle-size distributions and morphology, as well as by their biological properties in terms of cytotoxicity and antibacterial activity. Colloids containing both chitosan and hyaluronate showed only mild cytotoxicities, which were mainly governed by the concentration of conducting polyaniline in the colloid. Antibacterial activity of the samples, however, depended both on the type of polysaccharide and the ratio between the stabilizer and polyaniline mass. The colloid synthetized using 0.2 M aniline hydrochloride, 0.1 M ammonium persulfate, and 1 wt.% sodium hyaluronate of molecular weight of 1.8-2.1 × 106 exhibited the highest antibacterial activity against both gram positive and gram negative bacteria. This formulation, therefore, allowed for the formation of potentially stimuli-responsive antibacterial colloidal particles with low cytotoxicity.
Assuntos
Compostos de Anilina , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Coloides , Ácido Hialurônico/química , Compostos de Anilina/química , Compostos de Anilina/farmacologia , Animais , Coloides/química , Coloides/farmacologia , Escherichia coli/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Nanocompostos/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Today, the application of polyaniline in biomedicine is widely discussed. However, information about impurities released from polyaniline and about the cytotoxicity of its precursors aniline, aniline hydrochloride, and ammonium persulfate are scarce. Therefore, cytotoxicity thresholds for the individual precursors and their combinations were determined (MTT assay) and the type of cell death caused by exposition to the precursors was identified using flow-cytometry. Tests on fibroblasts revealed higher cytotoxicity of ammonium persulfate than aniline hydrochloride. Thanks to the synergic effect, both monomers in combination enhanced their cytotoxicities compared with individual substances. Thereafter, cytotoxicity of polyaniline doped with different acids (sulfuric, nitric, phosphoric, hydrochloric, and methanesulfonic) was determined and correlated with impurities present in respective sample (HPLC). The lowest cytotoxicity showed polyaniline doped with phosphoric acid (followed by sulfuric, methanesulfonic, and nitric acid). Cytotoxicity of polyaniline was mainly attributed to the presence of residual ammonium persulfate and low-molecular-weight polar substances. This is crucial information with respect to the purification of polyaniline and production of its cytocompatible form.