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1.
Carbohydr Polym ; 334: 122058, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38553243

RESUMO

Global public health is seriously threatened by thrombotic disorders because of their high rates of mortality and disability. Most thrombolytic agents, especially protein-based pharmaceuticals, have a short half-life in circulation, reducing their effectiveness in thrombolysis. The creation of an intelligent drug delivery system that delivers medication precisely and releases it under regulated conditions at nearby thrombus sites is essential for effective thrombolysis. In this article, we present a unique medication delivery system (MCRUA) that selectively targets platelets and releases drugs by stimulation from the thrombus' microenvironment. The thrombolytic enzyme urokinase-type plasminogen-activator (uPA) and the anti-inflammatory medication Aspirin (acetylsalicylic acid, ASA) are both loaded onto pH-sensitive CaCO3/cyclodextrin crosslinking metal-organic frameworks (MC) that make up the MCRUA system. c(RGD) is functionalized on the surface of MC, which is functionalized by RGD to an esterification reaction. Additionally, the thrombus site's acidic microenvironment causes MCRUA to disintegrate to release uPA for thrombolysis and aiding in vessel recanalization. Moreover, cyclodextrin-encapsulated ASA enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy. When used for thrombotic disorders, our drug delivery system (MCRUA) promotes thrombolysis, suppresses rethrombosis, and enhances biosafety with fewer hemorrhagic side effects.


Assuntos
Ciclodextrinas , Estruturas Metalorgânicas , Trombose , Humanos , Terapia Trombolítica , Ciclodextrinas/uso terapêutico , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Trombose/tratamento farmacológico , Aspirina/farmacologia , Oligopeptídeos
2.
Carbohydr Polym ; 328: 121703, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38220339

RESUMO

Arterial thrombosis is a critical thrombotic disease that poses a significant threat to human health. However, the existing clinical treatment of arterial thrombosis lacks effective targeting and precise drug release capability. In this study, we developed a system for targeted delivery and on-demand release in arterial thrombosis treatment. The carrier was constructed using chitosan (CS) and fucoidan (Fu) through layer-by-layer assembly, with subsequent surface modification using cRGD peptide. Upon encapsulation of urokinase-type plasminogen activator (uPA), the resulting therapeutic drug delivery system, uPA-CS/Fu@cRGD, demonstrated dual-targeting abilities towards P-selectin and αIIbß3, as well as pH and platelet-responsive release properties. Importantly, we have demonstrated that the dual targeting effect exhibits higher targeting efficiency at shear rates simulating thrombosed arterial conditions (1800 s-1) compared to single targeting for the first time. In the mouse common iliac artery model, uPA-CS/Fu@cRGD exhibited great thrombolytic capability while promoting the down-regulation of coagulation factors (FXa and PAI-1) and inflammatory factors (TNF-α and IL-6), thus improving the thrombus microenvironment and exerting potential in preventing re-occlusion. Our dual-target and dual-responsive, fucoidan-based macrovesicle represent a promising platform for advanced drug target delivery applications, with potential to prevent coagulation tendencies as well as improving thrombolytic and reducing the risk of re-occlusion.


Assuntos
Fibrinolíticos , Polissacarídeos , Trombose , Camundongos , Animais , Humanos , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Fibrinolíticos/química , Fibrinólise , Trombose/tratamento farmacológico , Terapia Trombolítica/métodos
3.
Carbohydr Polym ; 321: 121340, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37739514

RESUMO

The diabetic chronic wound healing is extremely restricted by issues such as hyperglycemia, excessive exudate and reactive oxygen species (ROS), and bacterial infection, causing significant disability and fatality rate. Herein, the chitosan/silk fibroin nanofibers-based hierarchical 3D sponge (CSSF-P/AuGCs) with effective exudate transfer and wound microenvironment modulation are produced by integrating cascade reactor (AuGC) into sponge substrates with parallel-arranged microchannels. When applied to diabetic wounds, the uniformly parallel-arranged microchannels endow CSSF-P/AuGCs with exceptional exudate absorption capacity, keeping the wound clean and moist; additionally, AuGCs efficiently depletes glucose in wounds to generate H2O2, which is then converted into HClO via cascade catalytic reaction to eliminate bacterial infection and reduce inflammation. Experiments in vitro demonstrated that the antibacterial activity of CSSF-P/AuGCs against S. aureus and E. coli was 92.7 and 94.27 %, respectively. Experiments on animals indicated that CSSF-P/AuGC could cure wounds in 11 days, displaying superior wound-healing abilities when compared to the commercial medication Tegaderm™. This versatile CSSF-P/AuGCs dressing may be an attractive choice for expediting diabetic wound healing with little cytotoxicity, providing a novel therapeutic method for establishing a favorable pathological microenvironment for tissue repair.


Assuntos
Quitosana , Diabetes Mellitus , Fibroínas , Nanofibras , Animais , Fibroínas/farmacologia , Escherichia coli , Peróxido de Hidrogênio , Staphylococcus aureus
4.
Int J Biol Macromol ; 253(Pt 4): 127000, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37739294

RESUMO

Optimal wound healing requires a wet microenvironment without over-hydration. Inspired by capillarity and transpiration, we have developed a sandwich-like fibers/sponge dressing with continuous exudate drainage to maintain appropriate wound moisture. This dressing is prepared by integrating a three-layer structure using the freeze-drying method. Layer I, as the side that contacts with the skin directly, consists of a hydrophobic silk fibroin membrane; Layer II, providing the pumping action, is made of superabsorbent chitosan-konjac glucomannan sponge; Layer III, accelerating evaporation sixfold compared to natural evaporation, is constructed with a graphene oxide soaked hydrophilic cellulose acetate membrane. Animal experiments showed that the composite dressing had superior wound-healing characteristics, with wounds decreasing to 24.8% of their original size compared to 28.5% for the commercial dressing and 43.2% for the control. The enhanced wound healing can be ascribed to the hierarchical porous structure serves as the fluid-driving factor in this effort; the hydrophilicity of a membrane composed of silk fibroin nanofibers is adjustable to regulate fluid-transporting capacity; and the photothermal effect of graphene oxide guarantees exudates that have migrated to the top layer to evaporate continuously. These findings indicate the unidirectional wicking dressing has the potential to become the next generation of clinical dressings.


Assuntos
Quitosana , Fibroínas , Animais , Fibroínas/química , Bandagens , Exsudatos e Transudatos , Quitosana/química , Seda
5.
Int J Biol Macromol ; 250: 126087, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37536416

RESUMO

Tissue adhesives have been widely used in biomedical applications. However, the presence of a hydrated layer on the surface of wet tissue severely hinders their adhesion capacities, resulting in ineffective wound treatment. To address this issue, a dry particle dressing (plas@SF/tann-hydro-pwd) capable of removing the hydrated layer and converting in situ to bioadhesives (plas@SF/tann-hydro-gel) was fabricated via simple physical mixing based on the hydrophobic-hydrogen bonding synergistic effect and Schiff-base reaction. It was found that the plas@SF/tann-hydro-gel bioadhesive, which was changed from plas@SF/tann-hydro-pwd dressing by adsorption of water, exhibited good wet adhesion to diverse biological tissues. In addition, the wet adhesion qualities of the plas@SF/tann-hydro-gel adhesive was studied under a variety of demanding conditions, including a wide range of temperatures, varying pH levels, highly concentrated salt solutions, and simulated fluids. Experiments on animals had showed that the adhesive plas@SF/tann-hydro-gel has superior wet adhesion qualities and superior wound healing properties compared to the commercial product Tegaderm™. This study develops a new wet-adhesion technique employing dry particle dressing to eliminate the hydrated layer over wet tissues for the in situ creation of gel bioadhesives for wound healing.

6.
Int J Biol Macromol ; 242(Pt 3): 124911, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37224899

RESUMO

Skin wound healing in dynamic environments remains challenging. Conventional gels are not ideal dressing materials for wound healing due to difficulties in completely sealing wounds and the inability to deliver drugs quickly and precisely to the injury. To tackle these issues, we propose a multifunctional silk gel that rapidly forms strong adhesions to tissue, has excellent mechanical properties, and delivers growth factors to the wound. Specifically, the presence of Ca2+ in the silk protein leads to a solid adhesion to the wet tissue through a chelation reaction with water-trapping behavior; the integrated chitosan fabric and CaCO3 particles ensure enhanced mechanical strength of the silk gel for better adhesion and robustness during wound repair; and the preloaded growth factor further promoted wound healing. The results showed the adhesion and tensile breaking strength were as high as 93.79 kPa and 47.20 kPa, respectively. MSCCA@CaCO3-aFGF could remedy the wound model in 13 days, with 99.41 % wound shrinkage without severe inflammatory responses. Due to strong adhesion properties and mechanical strength, MSCCA@CaCO3-aFGF can be a promising alternative to conventional sutures and tissue closure staples for wound closure and healing. Therefore, MSCCA@CaCO3-aFGF is expected to be a strong candidate for the next generation of adhesives.


Assuntos
Seda , Adesivos Teciduais , Adesivos , Cicatrização , Têxteis , Géis , Adesivos Teciduais/farmacologia
7.
Research (Wash D C) ; 6: 0150, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37223487

RESUMO

Efficient hemostasis during emergency trauma with massive bleeding remains a critical challenge in prehospital settings. Thus, multiple hemostatic strategies are critical for treating large bleeding wounds. In this study, inspired by bombardier beetles to eject toxic spray for defense, a shape-memory aerogel with an aligned microchannel structure was proposed, employing thrombin-carrying microparticles loaded as a built-in engine to generate pulse ejections for enhanced drug permeation. Bioinspired aerogels, after contact with blood, can rapidly expand inside the wound, offering robust physical barrier blocking, sealing the bleeding wound, and generating a spontaneous local chemical reaction causing an explosive-like generation of CO2 microbubbles, which provide propulsion thrust to accelerate burst ejection from arrays of microchannels for deeper and faster drug diffusion. The ejection behavior, drug release kinetics, and permeation capacity were evaluated using a theoretical model and experimentally demonstrated. This novel aerogel showed remarkable hemostatic performance in severely bleeding wounds in a swine model and demonstrated good degradability and biocompatibility, displaying great potential for clinical application in humans.

8.
Carbohydr Polym ; 315: 120967, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37230633

RESUMO

Uncontrolled bleeding is the leading cause of death, and the death risk of bleeding from coagulopathy is even higher. By infusing the relevant coagulation factors, bleeding in patients with coagulopathy can be clinically treated. However, there are not many emergency hemostatic products accessible for coagulopathy patients. In response, a Janus hemostatic patch (PCMC/CCS) with a two-layer structure of partly carboxymethylated cotton (PCMC) and catechol-grafted chitosan (CCS) was developed. Ultra-high blood absorption (4000 %) and excellent tissue adhesion (60 kPa) were both displayed by PCMC/CCS. The proteomic analysis revealed that PCMC/CCS has significantly contributed to the creative generation of FV, FIX, and FX, as well as to the substantial enrichment of FVII and FXIII, re-paving the initially blocked coagulation pathway of coagulopathy to promote hemostasis. The in vivo bleeding model of coagulopathy demonstrated that PCMC/CCS was substantially more effective than gauze and commercial gelatin sponge at achieving hemostasis in just 1 min. The study provides one of the first investigations on procoagulant mechanisms in anticoagulant blood conditions. Rapid hemostasis in coagulopathy will be significantly affected by the results of this experiment.


Assuntos
Quitosana , Hemostáticos , Humanos , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Quitosana/química , Proteômica , Hemostasia , Hemorragia/tratamento farmacológico , Catecóis/farmacologia
9.
Bioact Mater ; 16: 372-387, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35415282

RESUMO

Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature, thereby causing massive blood loss and significantly increased mortality. Inspired by the attack action of torpedoes, we synthesized microcluster (MC) colloidosomes equipped with magnetic-mediated navigation and "blast" systems to deliver hemostats into the cavity of vase-type wounds. CaCO3/Fe2O3 (CF) microparticles functionalized with Arg-Gly-Asp (RGD) modified polyelectrolyte multilayers were co-assembled with oppositely charged zwitterionic carbon dots (CDs) to form MC colloidosomes, which were loaded with thrombin and protonated tranexamic acid (TXA-NH3 +). The composite microparticles moved against blood flow under magnetic mediation and simultaneously disassembled for the burst release of thrombin stimulated by TXA-NH3 +. The CO2 bubbles generated during disassembly produced a "blast" that propelled thrombin into the wound cavity. Severe bleeding in a vase-type hemorrhage model in the rabbit liver was rapidly controlled within ∼60 s. Furthermore, in vivo subcutaneous muscle and liver implantation models demonstrated excellent biodegradability of MC colloidosomes. This study is the first to propose a novel strategy based on the principle of torpedoes for transporting hemostats into vase-type wounds to achieve rapid hemostasis, creating a new paradigm for combating trauma treatment.

10.
Biomater Sci ; 9(22): 7343-7378, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34672315

RESUMO

Traumatic hemorrhage can be a fatal event, particularly when large quantities of blood are lost in a short period of time. Therefore, hemostasis has become a crucial part of emergency treatment. For small wounds, hemostasis can be achieved intrinsically depending on the body's own blood coagulation mechanism; however, for large-area wounds, particularly battlefield and complex wounds, materials delivering rapid and effective hemostasis are required. In parallel with the constant progress in science, technology, and society, advances in hemostatic materials have also undergone various iterations by integrating new ideas with old concepts. There are various natural and synthetic hemostatic materials, including hemostatic powders, adhesives, hydrogels, and tourniquets, for the treatment of severe external trauma. This review covers the differences among the currently available hemostatic materials and comprehensively describes the hemostatic effects of different materials based on the underlying mechanisms. Finally, solutions for current issues related to trauma bleeding are discussed, and the prospects of hemostatic materials are proposed.


Assuntos
Hemostáticos , Coagulação Sanguínea , Hemorragia/terapia , Hemostasia , Hemostáticos/farmacologia , Humanos , Hidrogéis/farmacologia
11.
Bioact Mater ; 6(12): 4625-4639, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34095621

RESUMO

Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge. Therefore, we present a novel hemostatic strategy based on magnetic field-mediated guidance. The biphasic Janus magnetic particle (MSS@Fe2O3-T) comprised aggregates of α-Fe2O3 nanoparticles (Fe2O3 NPs) as the motion actuator, negatively modified microporous starch (MSS) as the base hemostatic substrate, and thrombin as the loaded hemostatic drug. Before application, the particles were first wrapped using NaHCO3 and then doped with protonated tranexamic acid (TXA-NH3 +), which ensured their high self-dispersibility in liquids. During application, the particles promptly self-diffused in blood by bubble propulsion and travelled to deep bleeding sites against reverse rushing blood flow under magnetic guidance. In vivo tests confirmed the superior hemostatic performance of the particles in perforating and inflected wounds ("V"-shaped femoral artery and "J"-shaped liver bleeding models). The present strategy, for the first time, extends the range of magnetically guided drug carriers to address the challenges in the hemorrhage control of perforating and inflected wounds.

12.
Mater Sci Eng C Mater Biol Appl ; 125: 112106, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33965113

RESUMO

Many approaches and technologies have been developed as treatments for microsporidian, infections but effective, broad-spectrum, and sustainable therapeutic approaches have not been found. Silver nanoparticles (AgNPs) have antimicrobial activity and are widely used against many different pathogens. AgNPs provide an opportunity to develop formulations that will control microsporidia. In this study, we synthesized AgNPs via a chemical reduction method and evaluated their formation, morphology, and stability using transmission electron microscopy (TEM) and ultraviolet spectroscopy analysis. We verified that AgNPs could disrupt the spore cell membrane and spore germination of microsporidia Nosema bombycis. This resulted in the release of microsporidia nucleic acids, proteins, and respiratory chain enzymes. The anti-microsporidia activity of AgNPs was studied by measuring the silkworm larvae survival rate and spore genome replication after microsporidia infection. AgNPs have anti-microsporidian activity and could be effective components of formulations for treating or preventing microsporidia infection.


Assuntos
Bombyx , Nanopartículas Metálicas , Nosema , Animais , Prata/farmacologia
13.
ACS Appl Mater Interfaces ; 13(19): 22225-22239, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33973760

RESUMO

Overexploitation of antibiotics increases the emergence of multidrug-resistant agents (MDRAs), which may potentially cause a global crisis with severe health consequences. Hence, there is great demand for next-generation antibacterial platforms based on antibiotic-free strategies or targeted therapies to mitigate the emergence of MDRAs. Herein, an all-in-one hollow nanoworm (A-Fe/AuAg@PDA) is developed with a core comprising citrate-capped Au-Ag nanoparticles (Cit-AuAg NPs) loaded with Fe2O3 and an l-arginine (L-Arg)-modified polydopamine (PDA) outer shell, possessing exceptional magnetic-targeting ability and a photothermal therapeutic effect. Following intravenous injection, A-Fe/AuAg@PDA can be precisely delivered to the targeted infection sites by an externally applied magnetic field. The in situ produced NO, together with Ag ions and reactive oxygen species, synergistically results in the highly effective elimination of in vivo bacterial infection. With the aid of functional worm-like A-Fe/AuAg@PDA nanocarriers possessing superior biocompatibility, the combination of magnetic guidance therapy and near-infrared-triggered in situ generation of NO may provide a novel approach for eradicating abscesses in the body. To our knowledge, this is the first study highlighting the magnetically guided delivery of worm-like nanocarriers for the antibiotic-free therapy of bacterial infections using in situ generated NO gas, which demonstrates high potential for application in clinical gas therapy.


Assuntos
Infecções Bacterianas/prevenção & controle , Sistemas de Liberação de Medicamentos , Magnetismo , Nanoestruturas , Óxido Nítrico/biossíntese , Animais , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Bioact Mater ; 6(9): 2956-2968, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33732966

RESUMO

The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics. Bacterial infections are detrimental to our life and health. To reduce the abuse of antibiotics and treat biofilm-related bacterial infections, a biomimetic nano-antibacterial system, RBCM-NW-G namely, that controls the release of antibiotics through near infrared was prepared. The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading, and then, biomimetics are applied with red blood cell membranes (RBCM). RBCM-NW-G, which retains the performance of RBCM, shows enhanced permeability and retention effects. Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection. In addition, the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility. Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect, silver iron, and antibiotics. Finally, by constructing a mouse infection model, the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.

15.
Int J Biol Macromol ; 148: 921-931, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982520

RESUMO

Timely antibacterial treatment of wounds reduces the probability of wound infection and promotes wound healing. However, the materials used to treat wounds often fail to provide both sterilization (especially for super bacteria) and moisture, and some may even cause secondary injury to the wound. In this study, gold nanoparticles (Au NPs) of average grain diameter of 3 ± 1 nm were prepared using egg white as the reductant. These particles showed no aggregation and pink fluorescence. Au NPs were mixed with gentamicin sulfate (GS) and loaded into a mixture of konjac glucomannan (KGM) and gelatin as wound dressing (KGM/Gelatin@Au NPs/GS). Antibacterial experiments showed that the Au NPs amplified the antibacterial activity of GS; Au NPs/GS efficiently eliminated bacteria, especially super bacteria. Cytotoxicity tests indicated that KGM/Gelatin@Au NPs/GS showed basically no cytotoxicity to L929 cells. In addition, KGM/Gelatin@Au NPs/GS possesses good water absorption, water retention, and enhanced mechanical properties, which can provide a moist environment for wounds and promote healing. In conclusion, our study showed that the antibacterial activity of KGM/Gelatin@Au NPs/GS is better than that of only GS and that it efficiently eliminated super bacteria. Therefore, KGM/Gelatin@Au NPs/GS can be used for killing superbugs, inhibiting bacterial growth, and promoting wound healing.


Assuntos
Antibacterianos/administração & dosagem , Gelatina , Gentamicinas/administração & dosagem , Ouro , Nanopartículas Metálicas , Proteínas , Cicatrização , Animais , Bandagens , Fenômenos Químicos , Ouro/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Proteínas/química , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia
16.
Carbohydr Polym ; 201: 522-531, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30241849

RESUMO

Hydrogels with self-healing capacity can undergo self-repair, establishing safer and longer-lasting products. Hydrogel wound dressings showing self-healing capacity can prolong the lifespan of the material and provide better wound protection. Therefore, in this study, Schiff base reactions (reversible imine linkages) were utilized to design injectable self-healing hydrogels with chitosan and konjac glucomannan. Oxidized konjac glucomannan was used to react with chitosan to form hydrogel. In addition to injectable, self-healing properties, the hydrogels also had adhesive and antibacterial properties, were biocompatible, and promoted wound healing. The inhibition rates of hydrogels against Staphylococcus aureus and Escherichia coli were 96% and 98%, respectively. In addition, microscopy and rheological analyses showed that the hydrogels healed within 4 h without additional exogenous stimulation. Finally, the developed hydrogels were injectable and significantly shortened wound recovery time in a full-thickness skin defect model. Thus, our findings established a novel hydrogel material that may have applications in wound healing.


Assuntos
Antibacterianos , Escherichia coli/crescimento & desenvolvimento , Hidrogéis , Pele , Staphylococcus aureus/crescimento & desenvolvimento , Adesivos Teciduais , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Linhagem Celular , Quitosana/química , Quitosana/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Mananas/química , Mananas/farmacologia , Camundongos , Pele/lesões , Pele/metabolismo , Pele/patologia , Suínos , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia
17.
Nanotechnology ; 29(42): 425603, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30070976

RESUMO

Wound infection caused by multiantibiotic-resistant bacteria has become a serious problem, and more effective antibacterial agents are required. Herein, we report the preparation of wound dressings using the biocompatible chitosan (CS) as a reducing and stabilizing agent in the synthesis of 2-mercapto-1-methylimidazole (MMT)-capped gold nanocomposites (CS-Au@MMT), with efficient antibacterial effects. The synergistic effects of AuNPs, MMT, and CS led to the disruption of bacterial membranes. After blending with gelatin, crosslinking with tannin acid, and freeze-drying, CS-gelatin (CS-Au@MMT/gelatin) dressing was prepared. It had good mechanical properties as well as efficient water absorption and retention capacities. It exhibited outstanding biocompatibility both in vitro and in a cell-based wound infection model. Moreover, the in vivo rabbit wound healing model revealed that the CS-Au@MMT/gelatin dressing possesses significant antibacterial potential against methicillin-resistant Staphylococcus aureus-associated wound infection. Therefore, the CS-Au@MMT/gelatin dressing described in this study may have huge potential in biomedical applications.


Assuntos
Antibacterianos/administração & dosagem , Bandagens , Nanopartículas Metálicas/administração & dosagem , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Materiais Biocompatíveis , Linhagem Celular , Quitosana/química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Gelatina/química , Ouro/química , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Coelhos , Infecção dos Ferimentos/microbiologia
18.
J Colloid Interface Sci ; 531: 269-281, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30036851

RESUMO

Biofilms that are widely associated with persistent bacterial infections impose a heavy burden on patients primarily due to their formidable resistance to conventional antiseptic drugs and local immune defense. Here, we successfully synthesized functional gold nanocomposites (CS-Au@MMT) by reducing chloroauric acid in the presence of biocompatible chitosan polymers with cationic amine and the small molecule 2-mercapto-1-methylimidazole (MMT). The cationic amine allowed transport of the CS-Au@MMT to the negatively charged sites at the surface of bacterial cells though electrostatic adhesion, with synergistic effects from the gold nanoparticles and MMT then exerting a strong bactericidal effect to inhibit biofilm formation. For established mature biofilms, CS-Au@MMT was able to adhere to the biofilm surface to render nearby bacterial cells inactive, resulting in biofilm rupture. This allowed CS-Au@MMT to penetrate through the biofilm, leading to sustained damage and achieving biofilm elimination. Furthermore, the nanocomposites efficiently inhibited infections induced by mature biofilm in vivo. These findings indicated that the CS-Au@MMT nanocomposites provide ease of synthesis and fabrication, high bactericidal effect, and low toxicity; thus, they show potential as biofilm-disrupting agents for biomedical and industrial applications.


Assuntos
Antibacterianos/farmacologia , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Ouro/farmacologia , Imidazóis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Linhagem Celular , Quitosana/química , Escherichia coli/fisiologia , Infecções por Escherichia coli/tratamento farmacológico , Ouro/química , Humanos , Imidazóis/química , Camundongos , Nanocompostos/química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/fisiologia
19.
Int J Biol Macromol ; 119: 505-516, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30059736

RESUMO

Developing highly active and green antibacterial agents for pathogens, especially multidrug-resistant superbugs, is vital for solving the problem of serious antibiotic resistance. Herein, we report a unique system of gold nanoparticles coated with chicken egg white (CEW) and 2-mercapto-1-methylimidazole (MMT) as a novel antibacterial agent. The CEW was used to prepare the gold nanoparticles as a commercially available reducing and stabilizing agent, and then the MMT self-assembled on the surface of nanoparticles. The resulting Au@CEW/MMT was found to be a highly efficient antibacterial agent, and the activity is mainly attributed to the synergistic effects of MMT and Au@CEW in undermining the bacterial membrane. Meanwhile, the studies of antibacterial activities and biocompatibility of Au@CEW/MMT with different ratios of MMT conjugation to Au@CEW confirmed that Au@CEW/MMT3 (MMT:HAuCl4 = 1:50) can maintain a balance between antibacterial properties and biocompatibility. Furthermore, in an in-vivo study using the rabbit model, gauze loaded with Au@CEW/MMT3 can effectively accelerate the healing of wounds infected with methicillin-resistant S. aureus and promote the formation of collagen. Therefore, this work illustrated a promising material with broad-spectrum antibacterial activities for preclinical applications in treating wound infections.


Assuntos
Bactérias/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Proteínas do Ovo/química , Ouro/farmacologia , Imidazóis/química , Nanopartículas Metálicas/química , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Bactérias/citologia , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Ouro/química , Ouro/toxicidade , Teste de Materiais , Camundongos , Coelhos
20.
Sci Rep ; 8(1): 1566, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29358730

RESUMO

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

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