RESUMEN
Introduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging. Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release. Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1. Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res.
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Alginatos , Caenorhabditis elegans , Nanogeles , Especies Reactivas de Oxígeno , Resveratrol , Animales , Caenorhabditis elegans/efectos de los fármacos , Resveratrol/farmacología , Resveratrol/química , Resveratrol/farmacocinética , Resveratrol/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Alginatos/química , Alginatos/farmacología , Nanogeles/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/farmacocinética , Polietilenglicoles/química , Polietilenglicoles/farmacología , Polietileneimina/química , Polietileneimina/farmacología , Polietileneimina/farmacocinética , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/farmacocinética , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinéticaRESUMEN
Purpose: Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention. Methods: In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine-indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff's base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG. Results: The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV-vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G-) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated. Conclusion: SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.
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Biopelículas , Verde de Indocianina , Rayos Infrarrojos , Fotoquimioterapia , Terapia Fototérmica , Polietilenglicoles , Biopelículas/efectos de los fármacos , Fotoquimioterapia/métodos , Animales , Polietilenglicoles/química , Verde de Indocianina/química , Verde de Indocianina/farmacología , Terapia Fototérmica/métodos , Ratones , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Polietileneimina/química , Polietileneimina/farmacología , Escherichia coli/efectos de los fármacos , Óxido Nítrico , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Especies Reactivas de Oxígeno/metabolismo , Nanopartículas/química , Tamaño de la PartículaRESUMEN
The innate immune system is an evolutionarily conserved pathogen recognition mechanism that serves as the first line of defense against tissue damage or pathogen invasion. Unlike the adaptive immunity that recruits T-cells and specific antibodies against antigens, innate immune cells express pathogen recognition receptors (PRRs) that can detect various pathogen-associated molecular patterns (PAMPs) released by invading pathogens. Microbial molecular patterns, such as lipopolysaccharide (LPS) from Gram-negative bacteria, trigger signaling cascades in the host that result in the production of pro-inflammatory cytokines. LPS stimulation produces a strong immune response and excessive LPS signaling leads to dysregulation of the immune response. However, dysregulated inflammatory response during wound healing often results in chronic non-healing wounds that are difficult to control. In this work, we present data demonstrating partial neutralization of anionic LPS molecules using cationic branched polyethylenimine (BPEI). The anionic sites on the LPS molecules from Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the lipid A moiety and BPEI binding create steric factors that hinder the binding of PRR signaling co-factors. This reduces the production of pro-inflammatory TNF-α cytokines. However, the anionic sites of Pseudomonas aeruginosa (P. aeruginosa) LPS are in the O-antigen region and subsequent BPEI binding slightly reduces TNF-α cytokine production. Fortunately, BPEI can reduce TNF-α cytokine expression in response to stimulation by intact P. aeruginosa bacterial cells and fungal zymosan PAMPs. Thus low-molecular weight (600 Da) BPEI may be able to counter dysregulated inflammation in chronic wounds and promote successful repair following tissue injury.
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Citocinas , Escherichia coli , Klebsiella pneumoniae , Lipopolisacáridos , Monocitos , Polietileneimina , Humanos , Citocinas/metabolismo , Polietileneimina/química , Polietileneimina/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/inmunología , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Escherichia coli/efectos de los fármacos , Peso Molecular , Moléculas de Patrón Molecular Asociado a Patógenos/metabolismo , Moléculas de Patrón Molecular Asociado a Patógenos/inmunologíaRESUMEN
Optically transparent glass with antifogging and antibacterial properties is in high demand for endoscopes, goggles, and medical display equipment. However, many of the previously reported coatings have limitations in terms of long-term antifogging and efficient antibacterial properties, environmental friendliness, and versatility. In this study, inspired by catfish and sphagnum moss, a novel photoelectronic synergy antifogging and antibacterial coating was prepared by cross-linking polyethylenimine-modified titanium dioxide (PEI-TiO2), polyvinylpyrrolidone (PVP), and poly(acrylic acid) (PAA). The as-prepared coating could remain fog-free under hot steam for more than 40 min. The experimental results indicate that the long-term antifogging properties are due to the water absorption and spreading characteristics. Moreover, the organic-inorganic hybrid of PEI and TiO2 was first applied to enhance the antibacterial performance. The Staphylococcus aureus and the Escherichia coli growth inhibition rates of the as-prepared coating reached 97 and 96% respectively. A photoelectronic synergy antifogging and antibacterial mechanism based on the positive electrical and photocatalytic properties of PEI-TiO2 was proposed. This investigation provides insight into designing multifunctional bioinspired surface materials to realize antifogging and antibacterial that can be applied to medicine and daily lives.
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Antibacterianos , Escherichia coli , Staphylococcus aureus , Titanio , Antibacterianos/farmacología , Antibacterianos/química , Titanio/química , Titanio/farmacología , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Polietileneimina/química , Polietileneimina/farmacología , Resinas Acrílicas/química , Resinas Acrílicas/farmacología , Pruebas de Sensibilidad Microbiana , Povidona/química , Propiedades de SuperficieRESUMEN
Biomedical devices are vulnerable to infections and biofilm formation, leading to extended hospital stays, high expenditure, and increased mortality. Infections are clinically treated via the administration of systemic antibiotics, leading to the development of antibiotic resistance. A multimechanistic strategy is needed to design an effective biomaterial with broad-spectrum antibacterial potential. Recent approaches have investigated the fabrication of innately antimicrobial biomedical device surfaces in the hope of making the antibiotic treatment obsolete. Herein, we report a novel fabrication strategy combining antibacterial nitric oxide (NO) with an antibiofilm agent N-acetyl cysteine (NAC) on a polyvinyl chloride surface using polycationic polyethylenimine (PEI) as a linker. The designed biomaterial could release NO for at least 7 days with minimal NO donor leaching under physiological conditions. The proposed surface technology significantly reduced the viability of Gram-negative Escherichia coli (>97%) and Gram-positive Staphylococcus aureus (>99%) bacteria in both adhered and planktonic forms in a 24 h antibacterial assay. The composites also exhibited a significant reduction in biomass and extra polymeric substance accumulation in a dynamic environment over 72 h. Overall, these results indicate that the proposed combination of the NO donor with mucolytic NAC on a polymer surface efficiently resists microbial adhesion and can be used to prevent device-associated biofilm formation.
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Acetilcisteína , Antibacterianos , Biopelículas , Escherichia coli , Óxido Nítrico , Staphylococcus aureus , Acetilcisteína/química , Acetilcisteína/farmacología , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Polietileneimina/química , Polietileneimina/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Pruebas de Sensibilidad Microbiana , Cloruro de Polivinilo/química , Donantes de Óxido Nítrico/química , Donantes de Óxido Nítrico/farmacologíaRESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease affecting the sinuses or nose. Persistent inflammatory responses can lead to tissue remodeling, which is a pathological characteristics of CRS. Activation of fibroblasts in the nasal mucosal stroma, differentiation and collagen deposition, and subepithelial fibrosis have been associated with CRS. OBJECTIVES: We aimed to assess the inhibitory effects of doxycycline and deoxycholic acid-polyethyleneimine conjugate (DA3-Doxy) on myofibroblast differentiation and extracellular matrix (ECM) production in nasal fibroblasts stimulated with TGF-ß1. METHODS: To enhance efficacy, we prepared DA3-Doxy using a conjugate of low-molecular-weight polyethyleneimine (PEI) (MW 1800) and deoxycholic acid (DA) and Doxy. The synthesis of the DA3-Doxy polymer was confirmed using nuclear magnetic resonance, and the critical micelle concentration required for cationic micelle formation through self-assembly was determined. Subsequently, the Doxy loading efficiency of DA3 was assessed. The cytotoxicity of Doxy, DA3, PEI, and DA-Doxy in nasal fibroblasts was evaluated using the WST-1 assay. The anti-tissue remodeling and anti-inflammatory effects of DA3-Doxy and DA3 were examined using real-time polymerase chain reaction (Real-time PCR), immunocytochemistry, western blot, and Sircol assay. RESULTS: Both DA3 and DA3-Doxy exhibited cytotoxicity at 10 µg/ml in nasal fibroblasts. Doxy partially inhibited α-smooth muscle actin, collagen types I and III, and fibronectin. However, DA3-Doxy significantly inhibited α-SMA, collagen types I and III, and fibronectin at 5 µg/ml. DA3-Doxy also modulated TGF-ß1-induced changes in the expression of MMP 1, 2, and 9. Nonetheless, TGF-ß1-induced expression of MMP3 was further increased by DA3-Doxy. The expression of TIMP 1 and 2 was partially reduced with 5 µg/ml DA3-Doxy. CONCLUSIONS: Although initially developed for the delivery of genetic materials or drugs, DA3 exhibits inhibitory effects on myofibroblast differentiation and ECM production. Therefore, it holds therapeutic potential for CRS, and a synergistic effect can be expected when loaded with CRS treatment drugs.
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Diferenciación Celular , Ácido Desoxicólico , Doxiciclina , Fibroblastos , Polietileneimina , Humanos , Polietileneimina/química , Polietileneimina/farmacología , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Diferenciación Celular/efectos de los fármacos , Doxiciclina/farmacología , Doxiciclina/química , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/citología , Actinas/metabolismoRESUMEN
In spite of tremendous efforts dedicated to addressing bacterial infections and biofilm formation, the post-antibiotic ear continues to witness a gap between the established materials and an easily accessible yet biocompatible antibacterial reagent. Here we show carbon dots (CDs) synthesized via a single hydrothermal process can afford promising antibacterial activity that can be further enhanced by exposure to light. By using citric acid and polyethyleneimine as the precursors, the photoluminescence CDs can be produced within a one-pot, one-step hydrothermal reaction in only 2 h. The CDs demonstrate robust antibacterial properties against both Gram-positive and Gram-negative bacteria and, notably, a considerable enhancement of antibacterial effect can be observed upon photo-irradiation. Mechanistic insights reveal that the CDs generate singlet oxygen (1O2) when exposed to light, leading to an augmented reactive oxygen species level. The approach for disruption of biofilms and inhibition of biofilm formation by using the CDs has also been established. Our findings present a potential solution to combat antibacterial resistance and offer a path to reduce dependence on traditional antibiotics.
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Antibacterianos , Biopelículas , Carbono , Puntos Cuánticos , Biopelículas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Carbono/química , Carbono/farmacología , Puntos Cuánticos/química , Pruebas de Sensibilidad Microbiana , Especies Reactivas de Oxígeno/metabolismo , Luz , Oxígeno Singlete/metabolismo , Polietileneimina/química , Polietileneimina/farmacología , Ácido Cítrico/química , Ácido Cítrico/farmacología , Bacterias Gramnegativas/efectos de los fármacosRESUMEN
Vascular transplantation is a common treatment for Cardiovascular disease (CVD). However, the mismatch of mechanical, structural, or microenvironmental properties of materials limits the clinical application. Therefore, the functional construction of artificial vessels or other blood contact materials remains an urgent challenge. In this paper, the composite nanofibers of polycaprolactone (PCL) with dopamine and polyethylenimine (PEI) coating are first prepared, which are further self-assembled by anticoagulant hirudin (rH) and antimicrobial peptide (AMP) of HHC36 through layer-by-layer (LBL) method. The results of FTIR and XPS analysis show that hirudin and AMP are successfully loaded on PEI-PDA/PCL nanofibers and the hydrophilicity is improved. They also show good mechanical properties that the ultimate tensile strength and elongation at break are better than natural blood vessels. The antibacterial results show that the antibacterial effect is still 93% against E. coli on the fifth day because of the stable and continuous release of HHC36 and rH. The performance of anticoagulant activity also exhibited the same results, which APTT is even 9.7s longer in the experimental group than the control group on the fifth day. The novel materials would be effectively solve the formation of thrombosis around artificial blood vessel grafts and the treatment of inflammation.
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Antibacterianos , Anticoagulantes , Escherichia coli , Nanofibras , Poliésteres , Anticoagulantes/farmacología , Anticoagulantes/química , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Poliésteres/química , Poliésteres/farmacología , Nanofibras/química , Humanos , Polietileneimina/química , Polietileneimina/farmacología , Hirudinas/farmacología , Hirudinas/química , Dopamina/farmacología , Dopamina/química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Resistencia a la TracciónRESUMEN
Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half-life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio-based hydrogel microspheres 'micro-cage', termed mPDA-PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)-functionalized mesoporous polydopamine (mPDA). This unique 'micro-cage' construct is designed to non-contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into 'micro-cage' along with wound exudation, and cationic mPDA-PEI immobilizes them inside the 'micro-cage' through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA-PEI@GelMA effectively mitigates pro-inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non-contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications.
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Trampas Extracelulares , Hidrogeles , Microesferas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Trampas Extracelulares/metabolismo , Trampas Extracelulares/efectos de los fármacos , Hidrogeles/química , Animales , Ratones , Humanos , Diabetes Mellitus Experimental , Modelos Animales de Enfermedad , Masculino , Indoles/química , Indoles/farmacología , Polímeros/química , Neutrófilos/metabolismo , Polietileneimina/química , Polietileneimina/farmacologíaRESUMEN
Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles. UDCA-PPG nanoparticles not only improve the solubility and dispersibility of UDCA, but also have good biocompatibility and stability, which significantly improve the delivery rate of UDCA. The results indicated that UDCA-PPG significantly reduced ROS levels, promoted cell proliferation, protected mitochondrial membrane potential, reduced DNA damage and reduced apoptosis in the DCA-induced cell model. In a mouse cholestasis model established by bile duct ligation (BDL), UDCA-PPG improved liver necrosis, fibrosis, and mitochondrial damage and reduced serum ALT and AST levels, which were superior to those in the UDCA-treated group. UDCA-PPG reduced the expression of the apoptosis-related proteins, Caspase-3 and Bax, increased the expression of Bcl-2, and reduced the expression of the oxidative stress-related proteins, NQO and HO-1, as well as the autophagy-related proteins LC3, p62 and p-p62. Therefore, UDCA-PPG can enhance the therapeutic effect of UDCA in cholestasis, by significantly improving drug dispersibility and stability, extending circulation time in vivo, promoting absorption, decreasing ROS levels, enhancing autophagy flow and inhibiting apoptosis via the Bcl-2/Bax signaling pathway.
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Apoptosis , Colestasis , Grafito , Hepatocitos , Nanocompuestos , Ácido Ursodesoxicólico , Grafito/química , Grafito/farmacología , Ácido Ursodesoxicólico/farmacología , Ácido Ursodesoxicólico/química , Animales , Apoptosis/efectos de los fármacos , Nanocompuestos/química , Ratones , Colestasis/tratamiento farmacológico , Colestasis/patología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Masculino , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Polietileneimina/química , Polietileneimina/farmacología , HumanosRESUMEN
The physiological problem of chronic inflammation and its associated pathologies attract ongoing attention with regard to methods for their control. Current systemic pharmacological treatments present problematic side effects. Thus, the possibility of new anti-inflammatory compounds with differing mechanisms of action or biophysical properties is enticing. Cationic polymers, with their ability to act as carriers for other molecules or to form bio-compatible materials, present one such possibility. Although not well described, several polycations such as chitosan and polyarginine, have displayed anti-inflammatory properties. The present work shows the ubiquitous laboratory transfection reagent, polyethylenimine (PEI) and more specifically low molecular weight branched PEI (B-PEI) as also possessing such properties. Using a RAW264.7 murine cell line macrophage as an inflammation model, it is found the B-PEI 700 Da as being capable of reducing the production of several pro-inflammatory molecules induced by the endotoxin lipopolysaccharide. Although further studies are required for elucidation of its mechanisms, the revelation that such a common lab reagent may present these effects has wide-ranging implications, as well as an abundance of possibilities.
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Lipopolisacáridos , Macrófagos , Polietileneimina , Animales , Polietileneimina/química , Polietileneimina/farmacología , Ratones , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Lipopolisacáridos/farmacología , Células RAW 264.7 , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/química , Biomarcadores/metabolismo , Línea CelularRESUMEN
Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease, which is responsible for enormous economic losses to the global pig industry. Although vaccination has been used to prevent PRV infection, the effectiveness of vaccines has been greatly diminished with the emergence of PRV variants. Therefore, there is an urgent need to develop anti-PRV drugs. Polyethylenimine (PEI) is a cationic polymer and has a wide range of antibacterial and antiviral activities. This study found that a low dose of 1 µg/mL of the 25-kDa linear PEI had significantly specific anti-PRV activity, which became more intense with increasing concentrations. Mechanistic studies revealed that the viral adsorption stage was the major target of PEI without affecting viral entry, replication stages, and direct inactivation effects. Subsequently, we found that cationic polymers PEI and Polybrene interfered with the interaction between viral proteins and cell surface receptors through electrostatic interaction to exert the antiviral function. In conclusion, cationic polymers such as PEI can be a category of options for defense against PRV. Understanding the anti-PRV mechanism also deepens host-virus interactions and reveals new drug targets for anti-PRV.IMPORTANCEPolyethylenimine (PEI) is a cationic polymer that plays an essential role in the host immune response against microbial infections. However, the specific mechanisms of PEI in interfering with pseudorabies virus (PRV) infection remain unclear. Here, we found that 25-kDa linear PEI exerted mechanisms of antiviral activity and the target of its antiviral activity was mainly in the viral adsorption stage. Correspondingly, the study demonstrated that PEI interfered with the virus adsorption stage by electrostatic adsorption. In addition, we found that cationic polymers are a promising novel agent for controlling PRV, and its antiviral mechanism may provide a strategy for the development of antiviral drugs.
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Antivirales , Herpesvirus Suido 1 , Polietileneimina , Electricidad Estática , Animales , Adsorción/efectos de los fármacos , Antivirales/química , Antivirales/farmacología , Herpesvirus Suido 1/efectos de los fármacos , Herpesvirus Suido 1/metabolismo , Polietileneimina/química , Polietileneimina/farmacología , Seudorrabia/tratamiento farmacológico , Seudorrabia/virología , Porcinos/virología , Enfermedades de los Porcinos/virologíaRESUMEN
Low molecular weight polyethylenimine (PEI) based lipopolymers become an attractive strategy to construct nonviral therapeutic carriers with promising transfection efficiency and minimal toxicity. Herein, this paper presents the design and synthesis of novel farnesol (Far) conjugated PEI, namely PEI1.2k-SA-Far7. The polymers had quick DNA complexation, effective DNA unpacking (dissociation), and cellular uptake abilities when complexed with plasmid DNA. However, they were unable to provide robust transfection in culture, indicating inability of Far grafting to improve the transfection efficacy significantly. To overcome this limitation, the commercially available polyanionic Trans-Booster additive, which is capable of displaying electrostatic interaction with PEI1.2k-SA-Far7, has been used to enhance the uptake of pDNA polyplexes and transgene expression. pDNA condensation was successfully achieved in the presence of the Trans-Booster with more stable polyplexes, and in vitro transfection efficacy of the polyplexes was improved to be comparable to that obtained with an established reference reagent. The PEI1.2k-SA-Far7/pDNA/Trans-Booster ternary complex exhibited good compatibility with cells and minimal hemolysis activity. This work demonstrates the exemplary potency of using additives in polyplexes and the potential of resultant ternary complexes for effective pDNA delivery.
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Técnicas de Transferencia de Gen , Polietileneimina , Polietileneimina/farmacología , Farnesol , ADN/genética , ADN/metabolismo , TransfecciónRESUMEN
The successful treatment of persistent and recurrent endodontic infections hinges upon the eradication of residual microorganisms within the root canal system, which urgently needs novel drugs to deliver potent yet gentle antimicrobial effects. Antibacterial photodynamic therapy (aPDT) is a promising tool for root canal infection management. Nevertheless, the hypoxic microenvironment within the root canal system significantly limits the efficacy of this treatment. Herein, a nanohybrid drug, Ce6/CaO2/ZIF-8@polyethylenimine (PEI), is developed using a bottom-up strategy to self-supply oxygen for enhanced aPDT. PEI provides a positively charged surface, which enables precise targeting of bacteria. CaO2 reacts with H2O to generate O2, which alleviates the hypoxia in the root canal and serves as a substrate for Ce6 under 660 nm laser irradiation, leading to the successful eradication of planktonic Enterococcus faecalis (E. faecalis) and biofilm in vitro and, moreover, the effective elimination of mature E. faecalis biofilm in situ within the root canal system. This smart design offers a viable alternative for mitigating hypoxia within the root canal system to overcome the restricted efficacy of photosensitizers, providing an exciting prospect for the clinical management of persistent endodontic infection.
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Biopelículas , Cavidad Pulpar , Enterococcus faecalis , Oxígeno , Fotoquimioterapia , Enterococcus faecalis/efectos de los fármacos , Fotoquimioterapia/métodos , Cavidad Pulpar/microbiología , Biopelículas/efectos de los fármacos , Oxígeno/química , Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Polietileneimina/química , Polietileneimina/farmacología , Nanopartículas/química , Animales , Compuestos de Calcio/química , Compuestos de Calcio/farmacología , ClorofilidasRESUMEN
Urinary tract infections (UTIs) are a significant cause of morbidity in healthcare systems and are prominently associated with applying urethral catheters, particularly in surgeries. Polyvinyl chloride (PVC) is extensively utilized in the fabrication of catheters. Biofilms, complex polymeric constructions, provide a protective milieu for cell multiplication and the enhancement of antibiotic resistance. Strategies to counteract biofilm development on medical apparatuses' surfaces incorporate antimicrobial agents such as N,N-dodecyl, and methyl polyethylenimine (DMPEI). This research endeavored to characterize the morphology of PVC and PVC-DMPEI surfaces utilizing Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) and to gauge hydrophobicity through contact angle measurements. Employing Escherichia coli, Staphylococcus aureus, and Candida albicans in adhesion assays enabled the assessment of DMPEI's efficacy in preventing microbial adherence to PVC. Butanol successfully solubilized 2 mg.mL-1 DMPEI without altering the PVC structure. SEM results substantiated the formation of a DMPEI layer on the PVC surface, which led to decreased surface roughness, as validated by AFM, and increased hydrophilicity, as demonstrated by contact angle evaluations. E. coli, S. aureus, and C. albicans exhibited significant adhesion reduction, 89.3%, 94.3%, and 86.6% on PVC-DMPEI surfaces. SEM visualizations confirmed reduced cellular colonization on PVC-DMPEI and highlighted considerable morphological modifications in E. coli. Consequently, DMPEI films effectively minimize the adhesion of E. coli, S. aureus, and C. albicans on PVC surfaces. DMPEI, with its potential as a protective coating for innovative medical devices, promises to inhibit biofilm adherence effectively.
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Escherichia coli , Polietileneimina , Polietileneimina/farmacología , Staphylococcus aureus , Catéteres , Biopelículas , Candida albicansRESUMEN
A significant problem related to the functioning of resin-based composites for dental fillings is secondary or recurrent caries, which is the reason for the need for repeated treatment. The cross-linked quaternary ammonium polyethylenimine nanoparticles (QA-PEI-NPs) have been shown to be a promising antibacterial agent against different bacteria, including cariogenic ones. However, little is known about the properties of dental dimethacrylate polymer-based composites enriched with QA-PEI-NPs. This research was carried out on experimental composites based on bis-GMA/UDMA/TEGDMA matrix enriched with 0.5, 1, 1.5, 2 and 3 (wt%) QA-PEI-NPs and reinforced with two glass fillers. The cured composites were tested for their adherence of Streptococcus Mutans bacteria, cell viability (MTT assay) with 48 h and 10-days extracts , degree of conversion (DC), water sorption (WSO), and solubility (WSL), water contact angle (CA), flexural modulus (E), flexural strength (FS), compressive strength (CS), and Vickers microhardness (HV). The investigated materials have shown a complete reduction in bacteria adherence and satisfactory biocompatibility. The QA-PEI-NPs additive has no effect on the DC, VH, and E values. QA-PEI-NPs increased the CA (a favorable change), the WSO and WSL (unfavorable changes) and decreased flexural strength, and compressive strength (unfavorable changes). The changes mentioned were insignificant and acceptable for most composites, excluding the highest antibacterial filler content. Probably the reason for the deterioration of some properties was low compatibility between filler particles and the matrix; therefore, it is worth extending the research by surface modification of QA-PEI-NPs to achieve the optimum performance characteristics.
Asunto(s)
Compuestos de Amonio , Nanopartículas , Metacrilatos , Polietileneimina/farmacología , Resinas Compuestas/farmacología , Polimerizacion , Ensayo de Materiales , Ácidos Polimetacrílicos , Agua , Antibacterianos/farmacología , BacteriasRESUMEN
Bacterial infections caused by Gram-negative pathogens, such as those in the family Enterobacteriaceae, are among the most difficult to treat because effective therapeutic options are either very limited or non-existent. This raises serious concern regarding the emergence and spread of multi-drug resistant (MDR) pathogens in the community setting; and thus, creates the need for discovery efforts and/or early-stage development of novel therapies for infections. Our work is directed towards branched polyethylenimine (BPEI) modified with polyethylene glycol (PEG) as a strategy for targeting virulence from Gram-negative bacterial pathogens. Here, we neutralize lipopolysaccharide (LPS) as a barrier to the influx of antibiotics. Data demonstrate that the ß-lactam antibiotic oxacillin, generally regarded as ineffective against Gram-negative bacteria, can be potentiated by 600 Da BPEI to kill some Escherichia coli and some Klebsiella pneumoniae. Modification of 600 Da BPEI with polyethylene glycol (PEG) could increase drug safety and improves potentiation activity. The ability to use the Gram-positive agent, oxacillin, against Gram-negative pathogens could expand the capability to deliver effective treatments that simplify, reduce, or eliminate some complicated treatment regimens.
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Escherichia coli , Klebsiella pneumoniae , Polietileneimina/farmacología , Virulencia , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Oxacilina/farmacología , Bacterias GramnegativasRESUMEN
OBJECTIVES: Ascorbic acid has many benefits to the skin. Numerous attempts to promote its topical delivery show great challenges since its chemical instability and poor skin impermeability. Microneedle delivery is a simple, safe, painless and effective means to deliver therapeutic or nourishing molecules into the skin. The purpose of this study was twofold: (a) to develop a new formulation of ascorbic acid-loaded microneedles to enhance ascorbic acid stability by investigating an optimal amount of polyethyleneimine as an additive to the dextran-based microneedle formulation and (b) to assess microneedle properties in terms of dissolving rate, skin penetration ability, biocompatibility and antimicrobial activity. METHODS: The microneedles formulated with ascorbic acid and varied polyethyleneimine concentrations were fabricated and subsequently tested for ascorbic acid stability using 2,2-diphenyl-1-picrylhydrazyl assay. The dissolution rate and skin penetration depth were investigated in porcine skin and the reconstructed human full-thickness skin model respectively. The skin irritation tests were done according to the Organisation for Economic Co-operation and Development Test Guideline No. 439. An antimicrobial disc susceptibility test was performed against Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis. RESULTS: Among varied amounts of 0%, 1.5%, 3.0% and 4.5% (w/v), the 3.0% polyethyleneimine showed the most desirable characteristics, including well-preserved shape integrity after demoulding, significantly improved stability of ascorbic acid (p < 0.001) from 33% to 96% antioxidant activity after 8 weeks of storage at 40°C, increased dissolving rate (p < 0.001) by being completely dissolved within 2 min after the skin insertion, passing skin penetration and biocompatibility tests as well as having a broad spectrum of antimicrobial property. CONCLUSION: With a safety profile and enhanced properties, the new formulation of ascorbic acid-loaded microneedles shows outstanding potential as commercially available cosmetics and healthcare products.
OBJECTIFS: L'acide ascorbique présente de nombreux avantages pour la peau. De nombreuses tentatives pour promouvoir sa délivrance topique présentent de grands défis en raison de son instabilité chimique et de sa faible imperméabilité cutanée. L'administration de micro-aiguilles est un moyen simple, sûr, indolore et efficace d'administrer des molécules thérapeutiques ou nourrissantes dans la peau. Le but de cette étude était double : a) développer une nouvelle formulation de microaiguilles chargées d'acide ascorbique pour améliorer la stabilité de l'acide ascorbique en étudiant une quantité optimale de polyéthylèneimine comme additif à la formulation de microaiguilles à base de dextrane ; et b) évaluer les propriétés des micro-aiguilles en termes de vitesse de dissolution, de capacité de pénétration cutanée, de biocompatibilité et d'activité antimicrobienne. MÉTHODES: Les microaiguilles formulées avec de l'acide ascorbique et des concentrations variées de polyéthylèneimine ont été fabriquées et ensuite testées pour la stabilité de l'acide ascorbique à l'aide d'un dosage de 2,2-diphényl-1-picrylhydrazyle. Le taux de dissolution et la profondeur de pénétration de la peau ont été étudiés dans la peau de porc et le modèle de peau humaine reconstruite de pleine épaisseur, respectivement. Les tests d'irritation cutanée ont été effectués conformément à la ligne directrice n° 439 de l'Organisation de coopération et de développement économiques. Un test de sensibilité du disque antimicrobien a été réalisé contre Escherichia coli, Staphylococcus aureus et Staphylococcusepidermidis. RÉSULTATS: Parmi des quantités variées de 0, 1,5, 3,0 et 4,5 % (p/v), la polyéthylèneimine à 3,0 % a montré les caractéristiques les plus souhaitables, notamment une intégrité de forme bien préservée après démoulage, une stabilité significativement améliorée de l'acide ascorbique (p ⟨ 0,001) de 33 % à 96 % d'activité antioxydante après 8 semaines de stockage à 40 °C, augmentation du taux de dissolution (p ⟨ 0,001) en étant complètement dissous dans les2 minutes suivant l'insertion de la peau, en passant les tests de pénétration cutanée et de biocompatibilité, ainsi qu'en ayant un large spectre de propriétés antimicrobiennes. CONCLUSION: Avec un profil d'innocuité et des propriétés améliorées, la nouvelle formulation de micro-aiguilles chargées d'acide ascorbique présente un potentiel exceptionnel en tant que produits cosmétiques et de soins de santé disponibles dans le commerce.
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Antiinfecciosos , Ácido Ascórbico , Animales , Porcinos , Humanos , Administración Cutánea , Ácido Ascórbico/farmacología , Polietileneimina/farmacología , Piel , Agujas , Inflamación , Antiinfecciosos/farmacología , Sistemas de Liberación de MedicamentosRESUMEN
This study examined the effectiveness of a DNA vaccine for S. agalactiae that was delivered by mannose-based polyethyleneimine (Man-PEI). The results showed that Man-PEI/pcDNA-Sip stimulated a higher serum antibody titer compared to control or other vaccine groups (p < 0.05). Additionally, it induced higher expression of immune-related genes, and increased activities of superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (AKP). Furthermore, the Man-PEI/pcDNA-Sip group showed an improved relative percent survival (RPS) of 85.71%. These results demonstrate the potential value of Man-PEI as a vaccine delivery vehicle, and suggest that it can be effective in boosting the immune protective rate induced by pcDNA-Sip vaccines.
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Cíclidos , Enfermedades de los Peces , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Vacunas de ADN , Animales , Polietileneimina/farmacología , Streptococcus agalactiae , Inmunidad , Enfermedades de los Peces/prevención & control , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/veterinariaRESUMEN
Reducing the cytotoxicity of cationic polymers is the major issue to their use as a gene delivery carrier. In this study, plasmids containing encoding vascular endothelial cell growth factor 165 and angiopoietin-1 were packaged with the conjugates of cationic fibroin (CSF) and polyethylenimine (PEI), instead of packaging pDNA with PEI alone, to prepare nanocomplexes (CSF+PEI)/pDNA. The complexes were loaded into a silk fibroin scaffold to enhance its function to induce microvascular network generation and dermal tissue regeneration. The results of transfecting EA.hy926 cells with the complexes in vitro showed that (CSF+PEI)/pDNA had a stronger transfection ability than PEI/pDNA. Importantly, compared with PEI as the gene carrier alone, the cell viability was significantly increased and the cytotoxicity was effectively reduced after the conjugate of CSF and PEI was used as the gene carrier. The results of angiogenesis in chick embryo chorioallantoic membranes showed that compared with scaffolds loaded with PEI/pDNA, the neovascularization ratio in scaffolds loaded with (CSF+PEI)/pDNA was significantly increased. In vivo experimental results of scaffolds implantation for full-thickness skin defects in SD rats showed that, compared with loading PEI/pDNA complex, loading (CSF+PEI)/pDNA complex in the scaffold more effectively promoted the formation of vascular network in the scaffold and accelerated the regeneration of dermal tissue. The gene delivery system established in this study has application potential not only in the regeneration of vascular-containing tissues, but also in tumor gene therapy.