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Polysaccharides display poor cell adhesion due to the lack of cell binding domains. This severely limits their applications in regenerative medicine. This study reports novel cross-linked pectin nanofibers with dramatically enhanced cell adhesion. The nanofibers are prepared by at first oxidizing pectin with periodate to generate aldehyde groups and then cross-linking the nanofibers with adipic acid dihydrazide to covalently connect pectin macromolecular chains with adipic acid dihydrazone linkers. The linkers may act as cell binding domains. Compared with traditional Ca2+-cross-linked pectin nanofibers, the pectin nanofibers with high oxidation/cross-linking degree exhibit much enhanced cell adhesion capability. Moreover, the cross-linked pectin nanofibers exhibit excellent mechanical strength (with Young's modulus â¼10 MPa) and much enhanced body degradability (degrade completely in 3 weeks or longer time). The combination of excellent cell adhesion capability, mechanical strength, and body degradability suggests that the cross-linked pectin nanofibers are promising candidates for in vivo applications such as tissue engineering and wound healing. This cross-linking strategy may also be used to improve the cell adhesion capability of other polysaccharide materials.
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Adipatos/química , Reagentes de Ligações Cruzadas/química , Nanofibras/química , Pectinas , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Camundongos , Pectinas/química , Pectinas/farmacologiaRESUMO
Pectin, a natural plant polysaccharide, holds great potential for biomedicine. Developing low molecular weight (Mw) pectin-based nanofibers is desirable for biomedical applications in which fast degradation and elimination of polymer from the body are required. Here, we report the first work on fabricating low Mw pectin-based nanofibers through electrospinning, among which the content of carrier polymer, poly(ethylene oxide) (PEO), can be minimized to 10%. Surfactant (Triton X-100), high polymer concentration and cosolvent were essential to electrospin bead-free nanofibers at low PEO content. The size of pectin nanofibers was dependent on polymer concentration and cosolvent. The presence of cosolvent inhibited the crystallization of PEO, but enhanced the crystallization of pectin. Meanwhile, glycerol as cosolvent could lead to phase separation of polymers. This work provides a new prospective for the fabrication of low Mw pectin nanofibers suitable for in vivo applications with the demand of fast degradation.
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Purpose: Conventional oral formulations for inflammatory bowel disease (IBD) treatment are less than satisfactory, due to the poor controllability of drug release and lack of specificity to the inflammation sites in the gastrointestinal (GI) tract. To overcome these limitations, we developed a multiple carbohydrate-based nanosystem with pH/ROS dual responsibility and charge-mediated targeting ability for IBD-specific drug delivery. Methods: In view of the overproduction of ROS and overexpression of cationic proteins in the inflammatory colon, the designed nanosystem was composed of oxidation-sensitive cyclodextrin (OX-CD), chitosan (CS) and pectin (AHP). OX-CD was utilized to load dexamethasone (DM) by the solvent evaporation method. CS and AHP with opposite charges were sequentially coated onto OX-CD to generate the nanosystems by the electrostatic self-assembly method. The physicochemical properties, stability, dual-sensitive drug release behavior, cytotoxicity, cellular uptake and anti-inflammatory activity were investigated in vitro. In vivo bio-distribution and therapeutic efficacy of the nanosystem were further evaluated in the ulcerative colitis (UC) mice. Results: The obtained AHP/CS/OX-CD-DM nanosystem (ACOC-DM) could maintain stability under the GI pH environments, and release drug in the inflammatory colon with pH/ROS sensitivity. Dual polysaccharide-coated ACOC-DM exhibited higher cellular uptake and anti-inflammatory efficacy in macrophages than single polysaccharide-coated CS/OX-CD-DM nanosystem (COC-DM). Orally administrated ACOC-DM could enhance inflammation targeting ability and therapeutic efficacy of DM in the UC mice. Conclusion: This carbohydrate-based nanosystem with pH/ROS dual sensitivity and inflammation targeting capacity may serve as a safe and versatile nanoplatform for IBD therapy.
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Anti-Inflamatórios , Quitosana , Colite Ulcerativa , Dexametasona , Pectinas , Animais , Colite Ulcerativa/tratamento farmacológico , Camundongos , Quitosana/química , Dexametasona/química , Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Dexametasona/farmacologia , Pectinas/química , Anti-Inflamatórios/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/farmacocinética , Ciclodextrinas/química , Ciclodextrinas/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Células RAW 264.7 , Concentração de Íons de Hidrogênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Portadores de Fármacos/química , Masculino , Nanopartículas/químicaRESUMO
Two pectic polysaccharides (WLBP-A3-c and WPOP-A-c) were isolated from traditional Chinese medicines Lilium brownii and Polygonatum odoratum, respectively. Monosaccharide composition, FT-IR, NMR and enzymatic analyses indicated that both WLBP-A3-c (59 kDa) and WPOP-A-c (33 kDa) contained homogalacturonan (HG), rhamnogalacturonan I (RG-I), and rhamnogalacturonan II (RG-II) domains, with mass ratios of 76.0: 17.2:6.8 and 76.8:10.6:12.6, respectively. Two RG-I domains WLBP-A3-c-DE1 and WPOP-A-c-DE1, correspondingly obtained from WLBP-A3-c and WPOP-A-c by enzymatic hydrolysis, were composed of repeating units of [â2)-α-L-Rhap-(1 â 4)-α-D-GalpA-(1â] with highly branched neutral sugar side chains at the O-4 position of Rhap, which contained arabinan, galactan, arabinogalactan I and II (AG-I and AG-II) side chains in different proportions. By comparison, WPOP-A-c exhibited higher scavenging effects against DPPH, ABTS and hydroxy radicals than WLBP-A3-c, probably because WPOP-A-c had higher contents of GalA residues and HG domains and lower molecular weight. Among three domains of WPOP-A-c, HG domain possessed the strongest activity in decreasing ROS production and promoting SOD activity, resulting in the effective protection of HepG2 cells against H2O2-induced oxidative stress. Our study provides evidence that pectins rich in HG domains from Lilium brownii and Polygonatum odoratum exhibit significant antioxidant effects, which hold potential for the application in the field of healthcare products.
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Lilium , Polygonatum , Antioxidantes/farmacologia , Peróxido de Hidrogênio , Espectroscopia de Infravermelho com Transformada de Fourier , Polissacarídeos/química , Pectinas/químicaRESUMO
Background: Pectins are a class of acidic polysaccharides with complex structures. Different pectin molecules are composed of different domains, which have an important impact on their biological activity. Objective: This study aimed to determine the structural features and the antioxidant activities of the pectic polysaccharides isolated from Veronica peregrina L. Methods: The polysaccharide was isolated from Veronica peregrina L by water extraction and fractionated by ion exchange chromatography and gel permeation chromatography. The structure features of the pectic polysaccharides were determined by Fourier transforminfrared spectroscopy (FT-IR) and Nuclear magnetic resonance (NMR). The antioxidant activities was evaluated by the DPPH, OH and ABTS radical scavenging ability. Results: WVPP-A2b and WVPP-A3b, with molecular weights of 48.7 × 104 and 77.6 × 104 kDa, respectively, contained homogalacturonan (HG), rhamnogalacturonan I (RG-I), and rhamnogalacturonan II (RG-II) domains with a mass ratio of 2.08:2.64:1.00 and 3.87:4.65:1:00, respectively. The RG-I domain contained an arabinogalactan II backbone and arabinans consisting of t-Araf, (1â5)-α-Araf, and (1â3,5)-α-Araf. WVPP-A3b also contained short chains consisting of the [t-Araf-(1â5)-α-Araf-(1â] structural unit. WVPP-A3b showed stronger ability to scavenge DPPH, hydroxyl, and ABTS radicals, which was potentially associated with its high content of galacturonic acid and presence of the HG domain. Conclusion: The results provide information for enhancing knowledge of the structureactivity relationship of pectic polysaccharides from V. peregrina and their potential application in the healthcare food field.
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CdHgTe/SiO(2) nanoparticles were prepared by SiO(2) capping on the surface of CdHgTe QDs. The characteristics, such as optical spectra, photostability, size and cell toxicity were investigated. The dynamic distribution of CdHgTe/SiO(2) nanoparticles was in vivo monitored by near infrared fluorescence imaging system. CdHgTe/SiO(2) nanoparticles acted as a novel fluorescence probe have a maximum fluorescence emission of 785 nm and high photo-stability. The hydrodynamic diameter of CdHgTe/SiO(2) nanoparticles could be adjusted to 122.3 nm. Compared to CdHgTe QDs, inhibitory effects of CdHgTe/SiO(2) nanoparticles on proliferation of HCT116 cells decreased to a certain extent. CdHgTe/SiO(2) nanoparticles had their specific dynamic distribution behavior, which provided new perspectives for bio-distribution of nanoparticles.
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Antineoplásicos/farmacologia , Compostos de Cádmio/farmacologia , Corantes Fluorescentes/farmacologia , Compostos de Mercúrio/farmacologia , Modelos Animais , Nanopartículas/química , Dióxido de Silício/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Cádmio/síntese química , Compostos de Cádmio/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Células HCT116 , Humanos , Compostos de Mercúrio/síntese química , Compostos de Mercúrio/química , Camundongos , Camundongos Endogâmicos , Tamanho da Partícula , Dióxido de Silício/síntese química , Dióxido de Silício/química , Relação Estrutura-Atividade , Propriedades de Superfície , Distribuição TecidualRESUMO
Pectin-based drug delivery systems hold great potential for oral insulin delivery, since they possess excellent gelling property, good mucoadhesion and high stability in the gastrointestinal (GI) tract. However, lack of enterocyte targeting ability and premature drug release in the upper GI tract of the susceptible ionic-crosslinked pectin matrices are two major problems to be solved. To address these issues, we developed folic acid (FA)-modified pectin nanoparticles (INS/DFAN) as insulin delivery vehicles by a dual-crosslinking method using calcium ions and adipic dihydrazide (ADH) as crosslinkers. In vitro studies indicated insulin release behaviors of INS/DFAN depended on COOH/ADH molar ratio in the dual-crosslinking process. INS/DFAN effectively prevented premature insulin release in simulated GI fluids compared to ionic-crosslinked nanoparticles (INS/FAN). At an optimized COOH/ADH molar ratio, INS/DFAN with FA graft ratio of 18.2% exhibited a relatively small particle size, high encapsulation efficiency and excellent stability. Cellular uptake of INS/DFAN was FA graft ratio dependent when it was at/below 18.2%. Uptake mechanism and intestinal distribution studies demonstrated the enhanced insulin transepithelial transport by INS/DFAN via FA carrier-mediated transport pathway. In vivo studies revealed that orally-administered INS/DFAN produced a significant reduction in blood glucose levels and further improved insulin bioavailability in type I diabetic rats compared to INS/FAN. Taken together, the combination of dual crosslinking and FA modification is an effective strategy to develop pectin nano-vehicles for enhanced oral insulin delivery.
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Diabetes Mellitus Experimental , Nanopartículas , Administração Oral , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Ácido Fólico/uso terapêutico , Insulina , Insulina Regular Humana/uso terapêutico , Pectinas/uso terapêutico , RatosRESUMO
CdHgTe-folate conjugates, acting as novel active-targeting fluorescence probes, were prepared by covalent conjugation of CdHgTe QDs and folic acid. Their characteristics, such as optical spectra, stability and cancer cell targeting were investigated in detail. The fluorescence wavelength of CdHgTe-folate conjugates was 790 nm and a full width at half-maximum (FWHM) of them was 50-70 nm. Their fluorescence stability could satisfy the need of long and continuous fluorescence imaging. The in vivo dynamic bio-distribution of CdHgTe-folate conjugates in S180 tumor beard mouse model was monitored by a NIR imaging system. The resultes indicated that CdHgTe-folate conjugates targeted to tumor effectively. The high fluorescence intensity together with targeting effect makes CdHgTe-folate conjugates promising candidates for imaging, monitoring and early diagnosis of cancer at molecular and cell level.
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Compostos de Cádmio/química , Detecção Precoce de Câncer/métodos , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Compostos de Mercúrio/química , Pontos Quânticos , Absorção , Animais , Carbodi-Imidas/química , Carcinossarcoma/diagnóstico , Carcinossarcoma/metabolismo , Corantes Fluorescentes/toxicidade , Ácido Fólico/toxicidade , Células HeLa , Humanos , Camundongos , Imagem Molecular , Fenômenos Ópticos , Sensibilidade e Especificidade , Espectrometria de Fluorescência , Succinimidas/químicaRESUMO
Silver-containing dressings are widely used for the treatment of infected wounds in clinics, but the potential risks of heavy metals are still a common concern. In this study, we prepared a type of electrospun starch nanofiber mat containing the antimicrobial peptide ε-poly-lysine (Starch-EPL) and compared its relevant properties with a representative silver-containing dressing 3M™ Tegaderm™ Alginate Ag (Alginate-Ag). SEM, FTIR and EDAX results show the two samples have similar fiber structures and are loaded with antibacterial agents. The comparison results indicate that the Starch-EPL nanofiber mat has equivalent permeability and absorbency with Alginate-Ag but higher mechanical property and wettability. Moreover, the Starch-EPL nanofiber mat has comparable antibacterial activity against both Gram-negative and Gram-positive bacteria with Alginate-Ag, but markedly better biocompatibility than that. The Starch-EPL nanofiber mat can inhibit the growth of bacteria for at least 14 days by sustainably releasing EPL, showing great potential as a long-term antibacterial dressing. All these results demonstrate that the Starch-EPL nanofiber mat may be a good candidate to replace the traditional silver-containing dressings.
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Nanofibras , Infecção dos Ferimentos , Antibacterianos/farmacologia , Bandagens , Humanos , Proteínas Citotóxicas Formadoras de Poros , PrataRESUMO
Silver nanoparticles (AgNPs) have a wide antimicrobial spectrum and low incidence of resistance. They have been widely incorporated into wound dressings for antimicrobial purpose. However, these wound dressings suffer from the accompanied cytotoxicity. It is important but challenging for them to reduce the cytotoxicity without compromising antimicrobial activity, while the affecting factors are unknown. In this work, we incorporated AgNPs into starch nanofiber mats with the in situ reduction method, and investigated the structure and property of the composite nanofiber mats in detail. We found that the cytotoxicity and antibacterial activity of the starch/AgNPs composite nanofiber mats are both affected by the release behavior of silver from the mats, while of various stages and governing factors. The cytotoxicity of the mats depends on the silver release rate at the early stage, which is governed by both the size and content of the AgNPs. The antibacterial activity is more related to the silver release rate at the later stage and is determined mainly by the content of AgNPs. By optimizing the size and content of AgNPs, we found a safe window and obtained starch/AgNPs composite nanofiber mats with good antibacterial activity and excellent cytocompatibility as well. The composite nanofiber mats also showed moderate wet strength (1-2 MPa), high liquid absorption capability (19-34 times of their own weights) and suitable vapor permeability [0.22-0.26 g/(cm2·24 h)]. These starch/AgNPs composite nanofiber mats are ideal candidates for the treatment of infected and exuding wounds.
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Anti-Infecciosos , Nanopartículas Metálicas , Nanofibras , Antibacterianos/farmacologia , PrataRESUMO
Its hydrophilic property and poor water resistance prevent the application of starch in electrospun nanofibers for biomedical applications. In this paper, we apply a periodate oxidation-adipic acid dihydrazide crosslinking strategy to electrospun starch nanofibers and develop a new nanofiber material with excellent mechanical strength, superior water resistance, and excellent cytocompatibility. The crosslinked starch nanofiber membranes exhibit a Young's modulus up to 2.65 MPa in the wet state, can maintain 91.0% of their initial mass after four weeks' incubation in simulated body fluid, and do not cause toxicity to L929 fibroblast cells. The control nanofibers prepared with a conventional glutaraldehyde crosslinking strategy show only a 60 kPa Young's modulus, retain only 31.9% of their initial mass after four weeks in simulated body fluid, and cause toxicity to cells. The crosslinked starch nanofibers with high mechanical strength, excellent water resistance and good biocompatibility are promising for biomedical applications.
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Reagentes de Ligações Cruzadas/química , Nanofibras/química , Amido/química , Adipatos/química , Animais , Adesão Celular , Proliferação de Células , Módulo de Elasticidade , Fibroblastos/metabolismo , Glutaral/química , Temperatura Alta , Camundongos , Microscopia Eletrônica de Varredura , Oxigênio/química , Ácido Periódico/química , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico , Resistência à Tração , ViscosidadeRESUMO
BACKGROUND: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. METHODS: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. RESULTS: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca2+/calmodulin-dependent protein kinase II. CONCLUSION: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.
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Pectin nanofiber mats are promising tissue engineering scaffolds but suffer from poor cell infiltration. In this study, gelatin, a collagen derived cell adhesive protein, was used to crosslink the electrospun nanofibers of periodate oxidized pectin. Cell culture experiment results demonstrated that cells were able to grow into the gelatin-crosslinked pectin nanofiber mats rather than only spread on mat surface. The nanofiber mats showed moderate mechanical strength, with a maximum tensile strength of up to 2.3 MPa, an ultimate tensile strain of up to 15%, and were capable of degrading gradually over 4 weeks or even longer periods in simulated body fluids. Thus, gelatin-crosslinked pectin nanofiber mats hold a great potential for soft tissue regeneration.
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Materiais Biocompatíveis/química , Nanofibras/química , Pectinas/química , Animais , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Gelatina/química , Camundongos , Propriedades de Superfície , Resistência à Tração , Engenharia TecidualRESUMO
Chronic wounds are of high incidence, difficult to heal, and can cause serious consequences if not properly treated. Doxycycline (DCH) is a broad-spectrum antibiotic and matrix metalloproteinases inhibitor, which has prominent efficacy for chronic wound treatment. Topical DCH treatment is the common administration route for chronic wounds in clinic but may result in low therapeutic efficacy and cause skin irritation at high DCH concentration, since it is difficult to control local drug concentration in the wounds and maintain the effective DCH concentration for a long time. In this study, we prepared DCH-encapsulated polylactide (DCH/PLA) nanofibers by a simple electrospinning method. Imaging studies showed that smooth and continuous DCH/PLA nanofibers with homogeneous DCH distribution were obtained at varied DCH loading content in the range of 5-30%. Mechanical property, water vapour permeability and absorbency of these nanofibers could meet the requirement as wound dressings. By adjusting DCH loading content, the wettability of the nanofibers could be transferred from hydrophobic to hydrophilic, and the release rate of DCH could be controlled in a sustained manner from three days to two weeks. Results of cytotoxicity and antibacterial test indicated that DCH/PLA nanofibers showed good cytocompatibility to L929 mouse fibroblast cells and exhibited positive antibacterial activity against Escherichia coli, suggesting its ability to treat/prevent infectious wounds. For full-thickness wound treatment of diabetic rats, DCH/PLA nanofiber mats can speed up wound healing to a higher extent than topical DCH treatment, due to the sustained release of DCH with less side effects. Our results indicate that DCH/PLA nanofiber mats hold great potential as wound dressings for chronic wound treatment.
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Doxiciclina/farmacologia , Nanofibras/química , Poliésteres/química , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Cristalização , Diabetes Mellitus Experimental/patologia , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Cinética , Masculino , Camundongos , Nanofibras/ultraestrutura , Permeabilidade , Ratos Sprague-Dawley , Vapor , MolhabilidadeRESUMO
Neutral polysaccharides such as konjac glucomannan, starch and pullulan are abundant in nature and have unique property. Their nanofibers hold great potential for biomedicine, which however, are seldom applied in the field due to the lack of crosslinking method. In this work, we report a periodate oxidation - adipic acid dihydrazide (ADH) crosslinking strategy to prepare robust and biocompatible neutral polysaccharide nanofibers. Neutral polysaccharides with adjacent dihydroxyl groups are firstly partially oxidized with periodate to give dialdehyde polysaccharides, and their electrospun nanofibers are then crosslinked with ADH to form dihydrazone crosslinkers. The resulting crosslinked neutral polysaccharide nanofibers exhibit high water resistance and excellent mechanical properties because of the high reactivity of Schiff base crosslinking reaction. Moreover, the crosslinked neutral polysaccharide nanofibers show good biocompatibility due to the low toxicity of ADH. These robust and biocompatible neutral polysaccharide nanofibers are expected to seek extensive applications in a variety of biomedical fields.
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Materiais Biocompatíveis/química , Mananas/química , Nanofibras/química , Adipatos/química , Adipatos/toxicidade , Animais , Materiais Biocompatíveis/toxicidade , Linhagem Celular Tumoral , Reagentes de Ligações Cruzadas/química , Mananas/toxicidade , Camundongos , Nanofibras/toxicidadeRESUMO
Nanofibers with well-dispersed Ag nanoparticles (AgNPs) are promising for some applications. Dispersion electrospinning is a straightforward preparation method but is suffered from the negative effects that the further treatments of nanofibers after electrospinning may bring to the dispersed AgNPs. In this study, we report a post reduction method to fabricate nanofibers with well-dispersed AgNPs. Crosslinked nanofibers of a hydrophilic polysaccharide, pectin, are used. When being immersed in the aqueous solution of AgNO3, the crosslinked pectin nanofibers swell, allowing Ag+ ions enter inside. The surrounding crosslinked pectin macromolecules functionalize as in situ reducing reagents to reduce Ag+ ions, nucleating the crystallization of AgNPs locally. X-ray diffraction characterizations indicate that the formed AgNPs are face-centered cubic crystalline. Results of optical imaging, UV-vis spectroscopy, scanning electron microscopy (SEM), electron dispersive spectrometry as well as transmission electron microscopy (TEM) indicate that the content and size of AgNPs increase with the increase of AgNO3 concentration and incubation time. SEM and TEM results show that the dispersion of the AgNPs does not affect the nanofibrous structure and size of the crosslinked pectin nanofibers. TEM results also demonstrate that AgNPs distribute homogeneously along both the length and diameter direction of nanofibers. The composite nanofibers can sustainably release silver for 4 weeks and inhibit the growth of Escherichia coli for 7 days, showing great potential as long-term antibacterial materials. The method may also be used to disperse AgNPs in other hydrophilic nanofibers which need further treatments after electrospinning.
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Polysaccharides including pectin, alginate and chitosan are fabricated into dressings of micrometer-scaled architecture (micro- fiber or particle) and widely applied in wound treatments clinically. This work characterized and compared the properties of electrospun nanofibrous dressings of these polysaccharides. We found that although the three polysaccharide nanofiber mats had comparable mechanical strength and vapour permeability, the pectinate nanofiber mat could absorb 1.2 times and 3.6 times more exudates than the alginate and chitosan nanofiber mats, respectively, within less time. Moreover, the pectinate nanofiber mat showed much higher antibacterial activity (73.1%) than the alginate and chitosan nanofiber mats (11.8% and 17.1%, respectively). Further examinations demonstrated that the superior absorbency and antibacterial activity of the pectinate nanofiber mat were associated with the moderate extent of swelling of pectinate nanofibers under hydrated conditions. All these results suggest that the pectinate nanofiber mat might be a superior wound dressing to the alginate and chitosan nanofiber mats.
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Antibacterianos/química , Bandagens , Nanofibras , Pectinas/química , Alginatos , Quitosana , Ácido Glucurônico , Ácidos HexurônicosRESUMO
Photodynamic therapy (PDT) has recently been proposed as an innovative approach to combat multi-drug resistant (MDR) bacteria. To improve the penetration depth of current PDT, a core-shell upconversion nanoparticle (UCNP) based PDT system, composed of a cationic N-octyl chitosan (OC) coated UCNP loaded with the photosensitizer zinc phthalocyanine (OC-UCNP-ZnPc), was constructed to enhance the antibacterial efficacy against MDR bacteria in deep tissue. The core-shell UCNPs displayed a higher upconversion fluorescence efficiency compared to the inner UCNP core. Dual antibacterial activities induced by chitosan and PDT-induced ROS were demonstrated, independent of the bacterial species. In particular, these nanoconstructs exhibited excellent antibacterial effects on the MDR bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and ß-lactamase-producing Escherichia coli. In vivo antibacterial therapy for murine MRSA-infected abscesses in the deep tissue (1 cm) strongly confirmed the outstanding anti-MRSA efficacy of OC-UCNP-ZnPc. Our results indicated that the OC-UCNP-ZnPc based PDT system triggered by deep-penetrating NIR light has a prominent antibacterial effect on MDR bacteria, which could be a promising strategy for deep-tissue infections.
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Antibacterianos/farmacologia , Quitosana , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Animais , Portadores de Fármacos , Feminino , Indóis/administração & dosagem , Isoindóis , Camundongos , Camundongos Endogâmicos ICR , NanopartículasRESUMO
We reported crosslinking of electrospun nanofibers of three representative pectins (high-methoxylated, low-methoxylated, low-methoxylated and amidated pectin) and characterization of the crosslinked nanofibers. One mono-crosslinking strategy and two dual-crosslinking strategies were developed. Mono-crosslinking is achieved using calcium ions (Ca2+) to crosslink carboxylate ions in galacturonic acid residues. Dual-crosslinking is achieved using covalent crosslinking reagents glutaraldehyde (GLU) or adipic acid dihydrazide (ADH) to further crosslink hydroxyl groups or carboxylate ions after Ca2+ crosslinking. Mechanical tests and degradation experiments indicated pectin structure affected mechanical and degradation properties of Ca2+-crosslinked nanofibers remarkably. Subsequent GLU crosslinking improved their mechanical strength moderately but did not inhibit their degradation, while subsequent ADH crosslinking improved their mechanical strength and slowed down their degradation dramatically. Cell studies demonstrated that most crosslinked pectin nanofibers were of no obvious cytotoxicity, and both ADH crosslinking and high degree of methoxylation facilitated cell adhesion and proliferation on pectin nanofiber mats.
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Nanofibers of natural polymers represent an essential class of materials in biomedicine. Pectin is a plant-sourced anionic polysaccharide widely used in food products and biomedicine owning to its abundance, biocompatibility and inherent bioactivity. However, current electrospun pectin nanofibers are suffered from high content of carrier polymer, which may lead to low integrity and mechanical strength as well as in vivo toxicity. We report here a strategy to reduce the content of carrier polymer, polyethylene oxide (PEO) in our study, in pectin nanofibers, via electrospinning at low loading followed with selective washing. With improved electrospinning condition, we first enabled electrospinning of pectin nanofibers at low PEO loading. Then the PEO was removed by washing with a selective solvent to give pectin nanofibers containing only 1.5% PEO. The strategy was versatile to pectins from various sources and of various degree of esterification. The pectin nanofibers exhibited Young's modulus as high as 358.5MPa. In view of their rich bioactivity, the pectin nanofibers of low content of carrier polymer are promising materials for a wide range of biomedical applications.