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In recent decades, the interest in responsive fibrous structures has surged, propelling them into diverse applications: from wearable textiles that adapt to their surroundings, to filtration membranes dynamically altering selectivity, these structures showcase remarkable versatility. Various stimuli, including temperature, light, pH, electricity, and chemical compounds, can serve as triggers to unleash physical or chemical changes in response. Processing methodologies such as weaving or knitting using responsive yarns, electrospinning, as well as coating procedures, enable the integration of responsive materials into fibrous structures. They can respond to these stimuli, and comprise shape memory materials, temperature-responsive polymers, chromic materials, phase change materials, photothermal materials, among others. The resulting effects can manifest in a variety of ways, from pore adjustments and altered permeability to shape changing, color changing, and thermal regulation. This review aims to explore the realm of fibrous structures, delving into their responsiveness to external stimuli, with a focus on temperature, light, and pH.
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The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP content and distribution within the textile fibres by morphological and chemical analysis, the samples were evaluated regarding their antimicrobial properties. The functionalised fabrics obtained via dip-pad-dry unveiled the most promising data, with 0.017 ± 0.013wt% ZnO NPs being mostly located at the fibre's surface and capable of total eradication of Staphylococcus aureus and Escherichia coli colonies within the tested 24 h (ISO 22196 standard), as well as significantly contributing (**** p < 0.0001) to the growth inhibition of the bacteriophage MS2, a surrogate of the SARS-CoV-2 virus (ISO 18184 standard). A three-layered structure was assembled and thermoformed to obtain facemasks combining the previously chosen NWF, and its resulting antimicrobial capacity, filtration efficiency and breathability (NP EN ISO 149) were assessed. The developed three-layered and multiscaled fibrous structures with antimicrobial capacities hold immense potential as active individual protection facemasks.
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The potential of nanoparticles as effective drug delivery systems combined with the versatility of fibers has led to the development of new and improved strategies to help in the diagnosis and treatment of diseases. Nanoparticles have extraordinary characteristics that are helpful in several applications, including wound dressings, microbial balance approaches, tissue regeneration, and cancer treatment. Owing to their large surface area, tailor-ability, and persistent diameter, fibers are also used for wound dressings, tissue engineering, controlled drug delivery, and protective clothing. The combination of nanoparticles with fibers has the power to generate delivery systems that have enhanced performance over the individual architectures. This review aims at illustrating the main possibilities and trends of fibers functionalized with nanoparticles, focusing on inorganic and organic nanoparticles and polymer-based fibers. Emphasis on the recent progress in the fabrication procedures of several types of nanoparticles and in the description of the most used polymers to produce fibers has been undertaken, along with the bioactivity of such alliances in several biomedical applications. To finish, future perspectives of nanoparticles incorporated within polymer-based fibers for clinical use are presented and discussed, thus showcasing relevant paths to follow for enhanced success in the field.
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The destruction of cells using the mechanical activation of magnetic nanoparticles with low-frequency magnetic fields constitutes a recent and interesting approach in cancer therapy. Here, we showed that superparamagnetic iron oxide nanoparticles as small as 6 nm were able to induce the death of pancreatic cancer-associated fibroblasts, chosen as a model. An exhaustive screening of the amplitude, frequency, and type (alternating vs. rotating) of magnetic field demonstrated that the best efficacy was obtained for a rotating low-amplitude low-frequency magnetic field (1 Hz and 40 mT), reaching a 34% ratio in cell death induction; interestingly, the cell death was not maximized for the largest amplitudes of the magnetic field. State-of-the-art kinetic Monte-Carlo simulations able to calculate the torque undergone by assemblies of magnetic nanoparticles explained these features and were in agreement with cell death experiments. Simulations showed that the force generated by the nanoparticles once internalized inside the lysosome was around 3 pN, which is in principle not large enough to induce direct membrane disruption. Other biological mechanisms were explored to explain cell death: the mechanical activation of magnetic nanoparticles induced lysosome membrane permeabilization and the release of the lysosome content and cell death was mediated through a lysosomal pathway depending on cathepsin-B activity. Finally, we showed that repeated rotating magnetic field exposure halted drastically the cell proliferation. This study established a proof-of-concept that ultra-small nanoparticles can disrupt the tumor microenvironment through mechanical forces generated by mechanical activation of magnetic nanoparticles upon low-frequency rotating magnetic field exposure, opening new opportunities for cancer therapy.
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Infection is a major issue in chronic wound care. Different dressings have been developed to prevent microbial propagation, but an effective, all-in-one (cytocompatible, antimicrobial and promoter of healing) solution is still to be uncovered. In this research, polyvinyl alcohol (PVA) nanofibrous mats reinforced with cellulose nanocrystal (CNC), at 10 and 20% v/v ratios, were produced by electrospinning, crosslinked with glutaraldehyde vapor and doped with specialized peptides. Crosslinking increased the mats' fiber diameters but maintained their bead-free morphology. Miscibility between polymers was confirmed by Fourier-transform infrared spectroscopy and thermal evaluations. Despite the incorporation of CNC having reduced the mats' mechanical performance, it improved the mats' surface energy and its structural stability over time. Pexiganan with an extra cysteine group was functionalized onto the mats via hydroxyl- polyethylene glycol 2-maleimide, while Tiger 17 was physisorbed to preserve its cyclic conformation. Antimicrobial assessments demonstrated the peptide-doped mat's effectiveness against Staphylococcus aureus and Pseudomonas aeruginosa; pexiganan contributed mostly for such outcome. Tiger 17 showed excellent capacity in accelerating clotting. Cytocompatibility evaluations attested to these mats' safety. C90/10 PVA/CNC mats were deemed the most effective from the tested group and, thus, a potentially effective option for chronic wound treatments.
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Anti-Infecciosos , Hemostáticos , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos , Celulose/farmacologia , Álcool de Polivinil/química , Estudos Prospectivos , CicatrizaçãoRESUMO
The extraction and exploration of cellulose-based polymers is an exciting area of research [...].
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The continued focus on improving the quality of human life has encouraged the development of increasingly efficient, durable, and cost-effective products in healthcare. Over the last decade, there has been substantial development in the field of technical and interactive textiles that combine expertise in electronics, biology, chemistry, and physics. Most recently, the creation of textile biosensors capable of quantifying biometric data in biological fluids is being studied, to detect a specific disease or the physical condition of an individual. The ultimate goal is to provide access to medical diagnosis anytime and anywhere. Presently, alcohol is considered the most commonly used addictive substance worldwide, being one of the main causes of death in road accidents. Thus, it is important to think of solutions capable of minimizing this public health problem. Alcohol biosensors constitute an excellent tool to aid at improving road safety. Hence, this review explores concepts about alcohol biomarkers, the composition of human sweat and the correlation between alcohol and blood. Different components and requirements of a biosensor are reviewed, along with the electrochemical techniques to evaluate its performance, in addition to construction techniques of textile-based biosensors. Special attention is given to the determination of biomarkers that must be low cost and fast, so the use of biomimetic materials to recognize and detect the target analyte is turning into an attractive option to improve electrochemical behavior.
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Técnicas Biossensoriais , Suor , Biomarcadores/análise , Técnicas Eletroquímicas , Etanol/análise , Humanos , Monitorização Fisiológica , Suor/químicaRESUMO
The rising threats to worldwide security (affecting the military, first responders, and civilians) urge us to develop efficient and versatile technological solutions to protect human beings. Soldiers, medical personnel, firefighters, and law enforcement officers should be adequately protected, so that their exposure to biological warfare agents (BWAs) is minimized, and infectious microorganisms cannot be spread so easily. Current bioprotective military garments include multilayered fabrics integrating activated carbon as a sorptive agent and a separate filtrating layer for passive protection. However, secondary contaminants emerge following their accumulation within the carbon filler. The clothing becomes too heavy and warm to wear, not breathable even, preventing the wearer from working for extended hours. Hence, a strong need exists to select and/or create selectively permeable layered fibrous structures with bioactive agents that offer an efficient filtering capability and biocidal skills, ensuring lightweightness, comfort, and multifunctionality. This review aims to showcase the main possibilities and trends of bioprotective textiles, focusing on metal-organic frameworks (MOFs), inorganic nanoparticles (e.g., ZnO-based), and organic players such as chitosan (CS)-based small-scale particles and plant-derived compounds as bioactive agents. The textile itself should be further evaluated as the foundation for the barrier effect and in terms of comfort. The outputs of a thorough, standardized characterization should dictate the best elements for each approach.
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In this research, we propose to engineer a nanostructured mat that can simultaneously kill bacteria and promote an environment conducive to healing for prospective wound care. Polyvinyl alcohol (PVA) and cellulose acetate (CA) were combined at different polymer ratios (100/0, 90/10, 80/20% v/v), electrospun and crosslinked with glutaraldehyde vapor. Crosslinked fibers increased in diameter (from 194 to 278 nm), retaining their uniform structure. Fourier-transform infrared spectroscopy and thermal analyses proved the excellent miscibility between polymers. CA incorporation incremented the fibers swelling capacity and reduced the water vapor and air permeabilities of the mats, preventing the excessive drying of wounds. The antimicrobial peptide cys-pexiganan and the immunoregulatory peptide Tiger 17 were incorporated onto the mats via polyethylene glycol spacer (hydroxyl-PEG2-maleimide) and physisorbed, respectively. Time-kill kinetics evaluations revealed the mats effectiveness against Staphylococcus aureus and Pseudomonas aeruginosa. Tiger 17 played a major role in accelerating clotting of re-calcified plasma. Data reports for the first time the collaborative effect of pexiganan and Tiger 17 against bacterial infections and in boosting hemostasis. Cytocompatibility data verified the peptide-modified mats safety. Croslinked 90/10 PVA/CA mats were deemed the most promising combination due to their moderate hydrophilicity and permeabilities, swelling capacity, and high yields of peptide loading.
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Anti-Infecciosos , Hemostáticos , Nanofibras , Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos , Celulose/análogos & derivados , Hemostasia , Nanofibras/química , Peptídeos , Álcool de Polivinil/química , Estudos ProspectivosRESUMO
One of the most important measures implemented to reduce SARS-CoV-2 transmission has been the use of face masks. Yet, most mask options available in the market display a passive action against the virus, not actively compromising its viability. Here, we propose to overcome this limitation by incorporating antiviral essential oils (EOs) within polycaprolactone (PCL) electrospun fibrous mats to be used as intermediate layers in individual protection masks. Twenty EOs selected based on their antimicrobial nature were examined for the first time against the Escherichia coli MS2 virus (potential surrogate of SARS-CoV-2). The most effective were the lemongrass (LGO), Niaouli (NO) and eucalyptus (ELO) with a virucidal concentration (VC) of 356.0, 365.2 and 586.0 mg/mL, respectively. PCL was processed via electrospinning, generating uniform, beadless fibrous mats. EOs loading was accomplished via two ways: (1) physisorption on pre-existing mats (PCLaEOs), and (2) EOs blending with the polymer solution prior to fiber electrospinning (PCLbEOs). In both cases, 10% v/v VC was used as loading concentration, so the mats' stickiness and overwhelming smell could be prevented. The EOs presence and release from the mats were confirmed by UV-visible spectroscopy (≈5257-631 µg) and gas chromatography-mass spectrometry evaluations (average of ≈14.3% EOs release over 4 h), respectively. PCLbEOs mats were considered the more mechanically and thermally resilient, with LGO promoting the strongest bonds with PCL (PCLbLGO). On the other hand, PCLaNO and PCLaELO were deemed the least cohesive combinations. Mats modified with the EOs were all identified as superhydrophobic, capable of preventing droplet penetration. Air and water-vapor permeabilities were affected by the mats' porosity (PCL < PCLaEOs < PCLbEOs), exhibiting a similar tendency of increasing with the increase of porosity. Antimicrobial testing revealed the mats' ability to retain the virus (preventing infiltration) and to inhibit its action (log reduction averaging 1). The most effective combination against the MS2 viral particles was the PCLbLGO. These mats' scent was also regarded as the most pleasant during sensory evaluation. Overall, data demonstrated the potential of these EOs-loaded PCL fibrous mats to work as COVID-19 active barriers for individual protection masks.
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Marine-derived chitosan (CS) is a cationic polysaccharide widely studied for its bioactivity, which is mostly attached to its primary amine groups. CS is able to neutralize reactive oxygen species (ROS) from the microenvironments in which it is integrated, consequently reducing cell-induced oxidative stress. It also acts as a bacterial peripheral layer hindering nutrient intake and interacting with negatively charged outer cellular components, which lead to an increase in the cell permeability or to its lysis. Its biocompatibility, biodegradability, ease of processability (particularly in mild conditions), and chemical versatility has fueled CS study as a valuable matrix component of bioactive small-scaled organic drug-delivery systems, with current research also showcasing CS's potential within tridimensional sponges, hydrogels and sutures, blended films, nanofiber sheets and fabric coatings. On the other hand, renewable plant-derived extracts are here emphasized, given their potential as eco-friendly radical scavengers, microbicidal agents, or alternatives to antibiotics, considering that most of the latter have induced bacterial resistance because of excessive and/or inappropriate use. Loading them into small-scaled particles potentiates a strong and sustained bioactivity, and a controlled release, using lower doses of bioactive compounds. A pH-triggered release, dependent on CS's protonation/deprotonation of its amine groups, has been the most explored stimulus for that control. However, the use of CS derivatives, crosslinking agents, and/or additional stabilization processes is enabling slower release rates, following extract diffusion from the particle matrix, which can find major applicability in fiber-based systems within ROS-enriched microenvironments and/or spiked with microbes. Research on this is still in its infancy. Yet, the few published studies have already revealed that the composition, along with an adequate drug release rate, has an important role in controlling an existing infection, forming new tissue, and successfully closing a wound. A bioactive finishing of textiles has also been promoting high particle infiltration, superior washing durability, and biological response.
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Antibacterianos/química , Quitosana/química , Extratos Vegetais/química , Antibacterianos/farmacologia , Organismos Aquáticos , Sistemas de Liberação de Medicamentos , Nanofibras/química , Nanopartículas/química , Extratos Vegetais/farmacologiaRESUMO
In the last decades, much research has been done to fasten wound healing and target-direct drug delivery. Hydrogel-based scaffolds have been a recurrent solution in both cases, with some reaching already the market, even though their mechanical stability remains a challenge. To overcome this limitation, reinforcement of hydrogels with fibers has been explored. The structural resemblance of fiber-hydrogel composites to natural tissues has been a driving force for the optimization and exploration of these systems in biomedicine. Indeed, the combination of hydrogel-forming techniques and fiber spinning approaches has been crucial in the development of scaffolding systems with improved mechanical strength and medicinal properties. In this review, a comprehensive overview of the recently developed fiber-hydrogel composite strategies for wound healing and drug delivery is provided. The methodologies employed in fiber and hydrogel formation are also highlighted, together with the most compatible polymer combinations, as well as drug incorporation approaches creating stimuli-sensitive and triggered drug release towards an enhanced host response.
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Nisin Z, an amphipathic peptide, with a significant antibacterial activity against Gram-positive bacteria and low toxicity in humans, has been studied for food preservation applications. Thus far, very little research has been done to explore its potential in biomedicine. Here, we report the modification of sodium alginate (SA) and gelatin (GN) blended microfibers, produced via the wet-spinning technique, with Nisin Z, with the purpose of eradicating Staphylococcus aureus-induced infections. Wet-spun SAGN microfibers were successfully produced at a 70/30% v/v of SA (2 wt%)/GN (1 wt%) polymer ratio by extrusion within a calcium chloride (CaCl2) coagulation bath. Modifications to the biodegradable fibers' chemical stability and structure were then introduced via crosslinking with CaCl2 and glutaraldehyde (SAGNCL). Regardless of the chemical modification employed, all microfibers were labelled as homogeneous both in size (≈246.79 µm) and shape (cylindrical and defect-free). SA-free microfibers, with an increased surface area for peptide immobilization, originated from the action of phosphate buffer saline solution on SAGN fibers, were also produced (GNCL). Their durability in physiological conditions (simulated body fluid) was, however, compromised very early in the experiment (day 1 and 3, with and without Nisin Z, respectively). Only the crosslinked SAGNCL fibers remained intact for the 28 day-testing period. Their thermal resilience in comparison with the unmodified and SA-free fibers was also demonstrated. Nisin Z was functionalized onto the unmodified and chemically altered fibers at an average concentration of 178 µg/mL. Nisin Z did not impact on the fiber's morphology nor on their chemical/thermal stability. However, the peptide improved the SA fibers (control) structural integrity, guaranteeing its stability for longer, in physiological conditions. Its main effect was detected on the time-kill kinetics of the bacteria S. aureus. SAGNCL and GNCL loaded with Nisin Z were capable of progressively eliminating the bacteria, reaching an inhibition superior to 99% after 24 h of culture. The peptide-modified SA and SAGN were not as effective, losing their antimicrobial action after 6 h of incubation. Bacteria elimination was consistent with the release kinetics of Nisin Z from the fibers. In general, data revealed the increased potential and durable effect of Nisin Z (significantly superior to its free, unloaded form) against S. aureus-induced infections, while loaded onto prospective biomedical wet-spun scaffolds.
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Alginatos/química , Antibacterianos/química , Antibacterianos/farmacologia , Reagentes de Ligações Cruzadas/química , Gelatina/química , Nisina/análogos & derivados , Staphylococcus aureus/efeitos dos fármacos , Materiais Biocompatíveis/química , Plásticos Biodegradáveis/química , Biopolímeros/química , Cloreto de Cálcio/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Glutaral/química , Cinética , Testes de Sensibilidade Microbiana , Nisina/química , Nisina/farmacologia , Porosidade , Solubilidade , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Água/químicaRESUMO
Nanogels were prepared in aqueous media without the use of any organic solvent via a simple polyelectrolyte complexation method between aminated pullulan and fucoidan followed by covalent crosslinking with genipin. Homogeneously distributed genipin crosslinked nanogels (G-PECs) were obtained with a mean hydrodynamic diameter of ~155 nm and zeta potential of 0.86 ± 4.35 mV. Their capacity to bind to human activated platelets was evaluated in vitro, as well as their cytocompatibility within human endothelial cells after 1 day of incubation up to 1000 µg/mL of G-PECs (94.56 ± 7.82% of viable cells). Additional hemolysis tests support the biocompatible character of the developed nanosystems (hemolysis rate of 2.09 ± 0.06% for 1000 µg/mL of G-PECs). Under acid conditions, the surface charge of G-PECs was tuned to around ~10 mV allowing miRNA incorporation via electrostatic interactions. G-PECs were able to promote miRNA delivery inside cells, as demonstrated by fluorescence microscopy images of labelled miRNA. With further studies to demonstrate the biological activity of delivered miRNA, these nanogels could be an interesting platform for miRNA-based therapeutics in atherothrombotic-related diseases thanks to the possibility to target over-expressed P-selectin.
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MicroRNAs , Selectina-P , Células Endoteliais , Humanos , Nanogéis , PolissacarídeosRESUMO
Chronic wounds (CW) create numerous entryways for pathogen invasion and prosperity, further damaging host tissue and hindering its remodeling and repair. Essential oils (EOs) exert quick and efficient antimicrobial (AM) action, unlikely to induce bacterial resistance. Cinnamon leaf and clove oils (CLO and CO) display strong AM activity, namely against Staphylococcus aureus and Pseudomonas aeruginosa. Chitosan (CS) is a natural and biodegradable cationic polysaccharide, also widely known for its AM features. CS and poly (vinyl alcohol) (PVA) films were prepared (ratio 30/70 w/w; 9 wt%) by the solvent casting and phase inversion method. The film's thermal stability and chemical composition data reinforced polymer blending and EO entrapment. Films were supplemented with 1 and 10 wt% of EO in relation to total polymeric mass. The film thickness and degree of swelling (DS) tended to increase with EO content, particularly with 10 wt % CLO (* p < 0.05). UV-visible absorbance scans in the 250-320 cm-1 region confirmed the successful uptake of CLO and CO into CS/PVA films, particularly with films loaded with 10 wt% EO that contained 5.30/5.32 times more CLO/CO than films supplemented with 1 wt% EO. AM testing revealed that CS films alone were effective against both bacteria and capable of eradicating all P. aeruginosa within the hour (*** p < 0.001). Still, loaded CS/PVA films showed significantly improved AM traits in relation to unloaded films within 2 h of contact. This study is a first proof of concept that CLO and CO can be dispersed into CS/PVA films and show bactericidal effects, particularly against S. aureus, this way paving the way for efficient CW therapeutics.
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New approaches to deal with the growing concern associated with antibiotic-resistant bacteria are emerging daily. Essential oils (EOs) are natural antimicrobial substances with great potential to mitigate this situation. However, their volatile nature, in their liquid-free form, has restricted their generalized application in biomedicine. Here, we propose the use of cellulose acetate (CA)/polycaprolactone (PCL) wet-spun fibers as potential delivery platforms of selected EOs to fight infections caused by Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Twenty EOs were selected and screened for their minimal inhibitory concentration (MIC), using the antibiotic ampicillin as positive control. The cinnamon leaf oil (CLO), cajeput oil (CJO), and the clove oil (CO) were the most effective EOs, against the Gram-positive (MIC < 22.38 mg/mL) and the Gram-negative (MIC < 11.19 mg/mL) bacteria. Uniform microfibers were successfully wet-spun from CA/PCL with an averaged diameter of 53.9 ± 4.5 µm, and then modified by immersion with CLO, CJO and CO at 2 × MIC value. EOs incorporation was confirmed by UV-visible spectroscopy, Fourier-transformed infrared spectroscopy, and thermal gravimetric analysis. However, while microfibers contained ampicillin at MIC (control) after the 72 h modification, the CLO, CO and CJO-loaded fibers registered ≈ 14%, 66%, and 76% of their MIC value, respectively. Data showed that even at small amounts the EO-modified microfibers were effective against the tested bacteria, both by killing bacteria more quickly or by disrupting more easily their cytoplasmic membrane than ampicillin. Considering the amount immobilized, CLO-modified fibers were deemed the most effective from the EOs group. These results indicate that CA/PCL microfibers loaded with EOs can be easily produced with increased antibacterial action, envisioning their use as scaffolding materials for the treatment of infections.
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Antibacterianos/química , Celulose/análogos & derivados , Portadores de Fármacos/química , Óleos Voláteis/química , Poliésteres/química , Acetatos/química , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Óleos Voláteis/administração & dosagem , Óleos Voláteis/farmacologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
The increased resistance of bacteria against conventional pharmaceutical solutions, the antibiotics, has raised serious health concerns. This has stimulated interest in the development of bio-based therapeutics with limited resistance, namely, essential oils (EOs) or antimicrobial peptides (AMPs). This study envisaged the evaluation of the antimicrobial efficacy of selected biomolecules, namely LL37, pexiganan, tea tree oil (TTO), cinnamon leaf oil (CLO) and niaouli oil (NO), against four bacteria commonly associated to nosocomial infections: Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa. The antibiotic vancomycin and silver nanoparticles (AgNPs) were used as control compounds for comparison purposes. The biomolecules were initially screened for their antibacterial efficacy using the agar-diffusion test, followed by the determination of minimal inhibitory concentrations (MICs), kill-time kinetics and the evaluation of the cell morphology upon 24 h exposure. All agents were effective against the selected bacteria. Interestingly, the AgNPs required a higher concentration (4000-1250 µg/mL) to induce the same effects as the AMPs (500-7.8 µg/mL) or EOs (365.2-19.7 µg/mL). Pexiganan and CLO were the most effective biomolecules, requiring lower concentrations to kill both Gram-positive and Gram-negative bacteria (62.5-7.8 µg/mL and 39.3-19.7 µg/mL, respectively), within a short period of time (averaging 2 h 15 min for all bacteria). Most biomolecules apparently disrupted the bacteria membrane stability due to the observed cell morphology deformation and by effecting on the intracellular space. AMPs were observed to induce morphological deformations and cellular content release, while EOs were seen to split and completely envelope bacteria. Data unraveled more of the potential of these new biomolecules as replacements for the conventional antibiotics and allowed us to take a step forward in the understanding of their mechanisms of action against infection-related bacteria.
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Fibrosis is characterized by a pathologic deposition of collagen I, leading to impaired function of organs. Tissue biopsy is the gold standard method for the diagnosis of fibrosis but this is an invasive procedure, subject to sampling errors. Several non-invasive techniques such as magnetic resonance imaging (MRI) using non-specific probes have been developed but they are not fully satisfying as they allow diagnosis at a late stage. In this study, collagelin, a collagen-binding peptide has been covalently linked using click chemistry to pegylated Ultra Small Super Paramagnetic Iron Oxide Nanoparticles (USPIO-PO-PEG-collagelin NPs) with the aim of diagnosing fibrosis at an early stage by MRI. USPIO-PO-PEG-collagelin NPs showed a high affinity for collagen I, two times higher than that of free collagelin whereas not peptide labeled USPIO NPs (USPIO-PO-PEG-yne) did not present any affinity. NPs were not toxic for macrophages and fibroblasts. Diffusion through collagen hydrogels concentrated at 3 and 10 mg mL-1 revealed a large accumulation of USPIO-PO-PEG-collagelin NPs within the collagen network after 72 hours, ca. 3 times larger than that of unlabeled USPIO, thereby evidencing the specific targeting of collagen I. Moreover, the quantity of USPIO-PO-PEG-collagelin NPs accumulated within hydrogels was proportional to the collagen concentration. Subsequently, the NPs diffusion through collagen hydrogels was monitored by MRI. The MRI T2 time relaxation decreased much more significantly with depth for USPIO-PO-PEG-collagelin NPs compared to unlabeled ones. Taken together, these results show that USPIO-PEG-collagelin NPs are promising as effective MRI nanotracers for molecular imaging of fibrosis at an early stage.
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Materiais Biocompatíveis/química , Fibrose/diagnóstico por imagem , Nanopartículas Magnéticas de Óxido de Ferro/química , Imageamento por Ressonância Magnética , Fragmentos de Peptídeos/química , Polietilenoglicóis/química , Sialoglicoproteínas/química , Animais , Materiais Biocompatíveis/síntese química , Células Cultivadas , Humanos , Camundongos , Imagem Molecular , Tamanho da Partícula , Células RAW 264.7 , Propriedades de SuperfícieRESUMO
Pullulan is a natural polysaccharide of potential interest for biomedical applications due to its non-toxic, non-immunogenic and biodegradable properties. The aim of this work was to synthesize cationic pullulan derivatives able to form complexes with microRNAs (miRNAs) driven by electrostatic interaction (polyplexes). Quaternized ammonium groups were linked to pullulan backbone by adding the reactive glycidyltrimethylammonium chloride (GTMAC). The presence of these cationic groups within the pullulan was confirmed by elemental analysis, Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H NMR). The alkylated pullulan was able to interact with miRNA and form stable polyplexes that were characterized regarding size, zeta potential and morphology. The presence of miRNA was confirmed by agarose gel electrophoresis and UV spectrophotometry. In vitro tests on human umbilical vein endothelial cells did not show any cytotoxicity after 1 day of incubation with nanosized polyplexes up to 200 µg/mL. QA-pullulan was able to promote miRNA delivery inside cells as demonstrated by fluorescence microscopy images of labelled miRNA. In conclusion, the formation of polyplexes using cationic derivatives of pullulan with miRNA provided an easy and versatile method for polysaccharide nanoparticle production in aqueous media and could be a new promising platform for gene delivery.
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Técnicas de Transferência de Genes , Glucanos/química , MicroRNAs/administração & dosagem , Cátions , Compostos de Epóxi/química , Glucanos/síntese química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Compostos de Amônio Quaternário/química , Eletricidade EstáticaRESUMO
In the last ten years, environmental consciousness has increased worldwide, leading to the development of eco-friendly materials to replace synthetic ones. Natural fibers are extracted from renewable resources at low cost. Their combination with synthetic polymers as reinforcement materials has been an important step forward in that direction. The sustainability and excellent physical and biological (e.g., biocompatibility, antimicrobial activity) properties of these biocomposites have extended their application to the biomedical field. This paper offers a detailed overview of the extraction and separation processes applied to natural fibers and their posterior chemical and physical modifications for biocomposite fabrication. Because of the requirements for biomedical device production, specialized biomolecules are currently being incorporated onto these biocomposites. From antibiotics to peptides and plant extracts, to name a few, this review explores their impact on the final biocomposite product, in light of their individual or combined effect, and analyzes the most recurrent strategies for biomolecule immobilization.