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Effective haemostatic materials can quickly control bleeding and achieve the purpose of saving patients' lives. In recent years, chitosan-based haemostatic materials have shown good haemostatic effects, but their application is limited because chitosan is almost insoluble in water. Carboxymethyl chitosan-based haemostatic materials can promote hemostasis by activating red blood cells and aggregating platelets. In addition, carboxymethyl chitosan can bind with Ca2+ to activate platelets and coagulation factors, and start endogenous coagulation pathways, which can adsorb fibrinogen in plasma to promote haemostasis. In this paper, the latest research progress of carboxymethyl chitosan-based haemostatic materials and their haemostatic mechanism were reviewed, in order to further strengthen the understanding of the haemostatic mechanism of carboxymethyl chitosan-based haemostatic materials, and provide new idea for the research and clinical application of carboxymethyl chitosan-based haemostatic materials.
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Humans , Hemostatics , Chitosan/pharmacology , Hemostasis , Blood Coagulation/physiology , HemorrhageABSTRACT
【Objective】 To develop a spray-on membrane dressing for wound repair containing platelet rich plasma (PRP) sodium alginate (SA)/agarose(AG)/carboxymethyl chitosan (CMCS). 【Methods】 SA/AG/ CMCS were mixed in different proportions to prepare biodegradable quick setting spray (BQSS) by blending film method, and the film-forming time, moisture retention and compression resistance of the prepared BQSS were tested. Then PRP and BQSS were mixed in the proportion of 3∶7, 4∶6, 5∶5, 6∶4 and 7∶3 to prepare PRP-BQSS spray film dressings. The film-forming time, moisture retention, compressive strength, porosity and slow-release effect of growth factors of PRP-BQSS spray film dressings were studied. 【Results】 In the preparation of BQSS compound spray film solution, when SA, AG, CMCS and sterile distilled water were 0.6∶0.6∶0.6∶98.2g, the film-forming time (7.73±0.31) s, moisture retention (75. 54±3.03) % and compression resistance (791.00±68.02) g of the spray-film dressing were the best. The basic properties of PRP-BQSS spray-on film dressings and the release of growth factors show that PRP-BQSS spray-on film dressings can exist in different forms, and with the decrease of PRP concentration percentage, its film-forming time, moisturizing performance and compressive strength showed an upward trend. When the PRP content is 30%, the porosity of the dressing is the highest, about(84.34±0.90)%. The release of platelet-derived growth factor-AA(PDGF-AA), platelet factor-4(PF-4) and transforming growth factor beta (TGF-β) was in a slow upward trend, and the release of the three growth factors was higher than that of PRP group in 48 hours. 【Conclusion】 The preparation method of PRP-BQSS spray film dressing designed in this study is simple and mild, and can form a film quickly, with good biological properties and better growth factor inhibition and sustained-release effect.
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Objective@#To explore effect on the remineralization of demineralized enamel surfaces with glycine-guided carboxymethyl chitosan (CMC)/amorphous calcium phosphate (ACP).@*Methods@# Remineralized solultion at different stages were prepared: ①reactive CMC/ACP (CMC/ACP nanoparticles treated with NaClO), ②reactive CMC/ACP+glycine; transmission electron microscopy was used to detect the morphology of the remineralized solution particles. Twenty teeth were randomly divided into two groups: group A and group B. Reactive CMC/ACP was applied to the enamel surface of group A and group B was treated with reactive CMC/ACP remineralization solution containing glycine. Scanning electron microscopy was used to detect the enamel surface morphology before and after remineralization, and nanoindentation was used to detect the mechanical strength (including nanoindentation depth, hardness and elastic modulus) of the enamel surface.@*Results@#Under a transmission electron microscope, the particles in the reactive CMC/ACP remineralization solution were smooth, and the increase in particle size was approximately 100-300 nm. After the addition of glycine, the particles in the reactive CMC/ACP remineralization solution particles showed a linear ordered arrangement, and microcrystals were formed in the solution 15 min later, with a crystal length of approximately 5-15 μm. Remineralization in group A was granular and heterogeneous. In group B, the crystal morphology of the demineralized enamel was homogeneous and ordered, similar to that of natural enamel. The nanoindentation depth of group B after remineralization was smaller than that of group A, and it was closest to that of natural enamel, there was no significant difference between group B and natural enamel in terms of the hardness and elastic modulus of the enamel surface after remineralization.@*Conclusion@# CMC/ACP nanoparticles treated with NaClO can rapidly and specifically form directional and ordered remineralization on the enamel surface of a model of glycine-guided rapid remineralization of enamel caries. The surface structure of remineralized enamel is similar to that of natural enamel in terms of nanoindentation depth, hardness and elastic modulus.
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ABSTRACT Purpose This study aimed to elaborate a hydrogel constituted by carboxymethyl chitosan (CMC), hyaluronic acid (HA) and silver (Ag) and to evaluate its healing effect on partial-thickness burn wounds experimentally induced in rats. Methods CMC was obtained by chitosan reacting with monochloroacetic acid. The carboxymethylation was confirmed by Fourier-transform infrared spectroscopy and hydrogen nuclear magnetic resonance (NMR). Scanning electron microscopy was used to determine the morphologicalcharacteristics of chitosan and CMC. After the experimental burn wound induction, the animals (n = 126) were treated with different CMC formulations, had their occlusive dressings changed daily and were followed through 7, 14 and 30 days. Morphometric, macroscopic and microscopic aspects and collagen quantification were evaluated. Results Significative wound contraction, granulation tissue formation, inflammatory infiltration and collagen fibers deposit throughout different phases of the healing process were observed in the CMC hydrogels treated groups. Conclusions The results showed that, in the initial phase of the healing process, the most adequate product was the CMC/HA/Ag association, while in the other phases the CMC/HA association was the best one to promote the healing of burn wounds.
Subject(s)
Burns/drug therapy , Chitosan , Wound Healing , Collagen , HydrogelsABSTRACT
BACKGROUND: Previous studies have shown that carboxymethyl chitosan/oxidized glucomannan composite sponge can be used as an excellent substrate for drug-loaded chronic wound dressings. OBJECTIVE: To prepare carboxymethyl chitosan/oxidized glucomannan/Panax notoginseng composite sponge and evaluate its physical and chemical properties and biocompatibility. METHODS: Oxidized glucomannan was prepared by sodium periodate oxidation. Panax notoginseng saponins were extracted from Panax notoginseng powder. Carboxymethyl chitosan and oxidized glucomannan were first added as mixed raw materials, and then added separately to account for mixing system 2%, 6%, 10% of Panax notoginseng saponins. Freeze-drying method was used to prepare carboxymethyl chitosan/oxidized glucomannan/Panax notoginseng composite sponge. Scanning electron microscope was utilized to observe the microstructure of the composite sponge. Porosity, steam permeability, total saponin release rate of Panax notoginseng, cell compatibility, antibacterial properties and acute systemic toxicity were detected. RESULTS AND CONCLUSION: (1) Scanning electron microscope showed that there were many pores in the composite sponge that were full and evenly distributed. The total saponins of Panax notoginseng were stably and evenly attached to the inner walls and joints of the pores of the sponge. (2) As the proportion of total saponins of Panax notoginseng increased, the water absorption rate, porosity, and steam permeability gradually increased. (3) The vast majority of the total saponins of Panax notoginseng in the three kinds of composite sponges could be efficiently released in 13 hours in vitro. (4) Within 3 days after in vitro culture, the proliferation rate of fibroblasts was more than 95%. (5) Three kinds of compound sponges have an inhibitory effect on E. coli and Staphylococcus aureus, but do not have acute systemic toxicity. (6) The results show that carboxymethyl chitosan/oxidized glucomannan/Panax notoginseng composite sponge is expected to be an excellent medical chronic wound dressing.
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@#In this study, in vitro cytotoxicity of carboxymethyl chitosan-rhein conjugate(CR conjugate)and paclitaxel-loaded carboxymethyl chitosan-rhein polymeric micelles(PTX/CR PMs)was evaluated by MTT method in MCF-7 cells. The results showed that CR conjugate displayed good security; PTX/CR PMs in 24 h showed better antitumor activity than Taxol® . Environment-responsive fluorescent probe P4 was used to determine the cellular uptake of PTX/CR PMs in MCF-7 cells. The results also showed that P4 and PTX co-loaded carboxymethyl chitosan-rhein polymeric micelles ［(P4+PTX)/CR PMs］ could be taken up by MCF-7 cells. There was no difference between(P4+PTX)/CR PMs group and(P4+PTX)/CR PMs with verapamil group, suggesting that CR PMs could protect fluorescent probe and/or drugs in their cores avoiding efflux by P-glycoprotein. These results will contribute to in vivo study of CR conjugate and PTX/CR PMs in the future.
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OBJECTIVE: To prepare paclitaxel loaded D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)-modified carboxymethyl chitosan-rhein polymeric micelles (PTX/TPGS-CR PMs) and preliminarily evaluate their performance. METHODS: PTX/TPGS-CR PMs was prepared by dialysis method, and the preparation procedure of PTX/TPGS-CR PMs was optimized by single factor with the drug loading, encapsulation rate and particle size as the indicators, then the optimized preparation procedure was verified. The safety of PTX/TPGS-CR PMs was initially investigated by the hemolysis test and the vascular irritation test. The cytotoxicity of PTX/TPGS-CR PMs in Hela cells was studied by MTT assay. Cell uptake experiments were performed by laser confocal microscopy and flow cytometry to investigate the uptake of PTX/TPGS-CR PMs by Hela cells. RESULTS: The particle size and PDI of PTX/TPGS-CR PMs prepared by the optimized preparation were (197.3±4.4) nm and (0.131±0.021), respectively. The Zeta potential was (-31.8±0.5) mV. The drug loading and encapsulation efficiency were (48.20±3.03)% and (87.26±4.91)%, respectively. The hemolytic test results showed that the hemolysis rate was less than 1.71%. No obvious irritation was observed after intravenous injection. The cytotoxicity of PTX/TPGS-CR PMs in Hela cells was concentration-and time-dependent. Cell uptake experiments showed that PTX/TPGS-CR PMs could be efficiently uptake by Hela cells. CONCLUSION: The PTX/TPGS-CR PMs has high drug loading and encapsulation efficiency, good safety. And they exhibite slightly better antitumor activity in vitro than Taxol®.
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OBJECTIVE@#This study aimed to optimize the preparation of carboxymethyl chitosan/sodium alginate (CMCS/OSA) compound hydrogels. This study also aimed to investigate the applicability of the hydrogels in cartilage tissue engi-neering.@*METHODS@#Three groups of CMCS/OSA composite hydrogels with amino-to-aldehyde ratios of 2∶1, 1∶1 and 1∶2 were prepared. The microstructure, physical properties, and cell biocompatibility of the three groups of CMCS/OSA com-posite hydrogels were evaluated. Samples were subjected to scanning electron microscopy, rheological test, adhesion tension test, swelling rate test, and cell experiments to identify the CMCS/OSA composite hydrogel with the cross-linking degree that can meet the requirements for scaffolds in cartilage tissue engineering.@*RESULTS@#The experimental results showed that the CMCS/OSA hydrogel with a amine-to-aldhyde ratio of 1∶1 had good porosity, suitable gelling time, strong adhesive force, stable swelling rate, and good cellular biocompatibility.@*CONCLUSIONS@#The CMCS/OSA compound hydrogel prepared with a 1∶1 ratio of amino and aldehyde groups has potential applications in cartilage tissue engineering.
Subject(s)
Alginates , Cartilage , Chitosan , Hydrogels , Tissue EngineeringABSTRACT
Chitosan is a biocompatible and biodegradable mucoadhesive polymer with unique advantages, such as the distinct trait of opening the junctions to allow paracellular transport of antigen and good tolerability. However, the poor solubility of chitosan in neutral or alkalinized media has restricted its applications in the pharmaceutical field. Chitosan can be easily carboxymethylated to improve its solubility in aqueous media, while its biodegradability and biocompatibility are preserved. Apart from this, carboxymethyl chitosan (CMCS) can be easily processed into nanoparticles which highlight its suitability and extensive usage for preparing different drug delivery formulations. The present study deals with the development and characterization of a delivery system based on CMCS nanoparticles using ovalbumin as model protein. We demonstrated that ovalbumin loaded nanoparticles were successfully synthetized using calcium chloride as a cross-linker by ionic gelation. The nanoparticles exhibited an average size of approximately 169 nm and presented a pseudo-spherical shape. The nanoparticles size increased according to the addition of CaCl2 due to the strong electrostatic attraction. During storage the nanoparticles size increased was attributed to swelling and aggregation. The loading efficiency of ovalbumin was found to be 17%. Confocal microscopy clearly showed the association between ovalbumin and CMCS chains into nanoparticles. Therefore, we suggest these nanoparticles can be considered as an attractive and promising carrier candidate for proteins and antigens. The major challenge that limits the use of such carriers is their instability in an aqueous medium. Thus, the next step of this work was to determine the robustness of several formulations using distinct freeze-drying protocols. This study demonstrated that mannitol in concentration of 10% (w/v) is well suited to preserve ovalbumin loaded CMCS nanocapsules from aggregation during lyophilization and subsequent reconstitution. Importantly, the results showed that an annealing step has a huge impact on porosity of freeze-dried cake by nearly complete crystallization of mannitol, once the crystalline matrix prevents the partial collapse and the formation of larger pores observed without annealing. Therefore, the usual observation that annealing increases the pore size due to growth of ice crystal size does not always apply, at least when crystallization of solute is involved. Since all characterizations and stability studies had been performed, the main purpose of this study was to develop a stable antigen delivery system for oral immunization using CMCS and inactivated rabies virus (RV) as the antigen. RV loaded nanoparticles was found to enhance both systemic (IgG) and local (IgA) immune responses against RV after oral delivery in mice. The effective doses 50% were 50-times higher than the negative controls, indicating that the immune response started only after the third boosting dose. Furthermore, enough neutralizing antibodies was produced to be protected against the harmful effects of the rabies virus. It is therefore concluded, that the CMCS nanoparticles formulated in this study, are suitable for oral vaccine delivery, and can be suggested as a promising delivery system for a diverse range of antigens as well as a gene/protein delivery system, especially for those positively charged. Since several approaches show that effective intervention in airway allergic inflammation can be achieved with allergen-activated interleukin-10-secreting cells, the final part of this work was dedicated to assessing whether IL-10 loaded chitosan nanoparticles (IL10-CSNPs) could be used as a possible inhalable therapeutic tool for preventing exacerbations in asthmatic patients. As positive controls, we also assess whether interleukin 17A and interleukin 9 have the ability to stimulate human airway smooth muscle (HASM) cell contractility using magnetic twisting cytometry (MTC). Significant decreased baseline cell stiffness was observed in HASM cells pre-treated with IL-10, but not with IL10-CSNPs, whereas treatment with IL-17A significantly enhanced baseline cell stiffening. Our findings reveal a previously unknown mechanism underlying immunotherapy for prevention and treatment of asthma
A quitosana é um polímero mucoadesivo biocompatível e biodegradável, com vantagens únicas, tais como a característica distinta de abrir as junções que permitim o transporte paracelular de antígenos e boa tolerabilidade. No entanto, sua baixa solubilidade em meios neutros ou alcalinizados tem restringido suas aplicações no campo farmacêutico. A quitosana pode ser facilmente carboximetilada para melhorar de sua solubilidade em meios aquosos, enquanto sua biodegradabilidade e biocompatibilidade são preservadas. Além disso, a carboximetilquitosana (CMCS) pode ser facilmente processada na forma de nanopartículas, o que destaca sua adequabilidade para uso extensivo no preparo de sistemas de delivery de medicamentos. O presente estudo trata do desenvolvimento e caracterização de um sistema de delivery baseado em nanopartículas de CMCS utilizando ovalbumina como proteína modelo. Nós demonstramos que as nanopartículas carregadas com ovalbumina foram sintetizadas com sucesso utilizando cloreto de cálcio como agente de reticulação por gelificação iônica. As nanopartículas exibiram um tamanho médio de aproximadamente 169 nm e apresentaram uma forma pseudo-esférica. O tamanho das nanopartículas aumentou de acordo com a adição de CaCl2 devido à forte atração eletrostática. Durante o armazenamento, o tamanho aumentado das nanopartículas foi atribuído a incorporação de água e agregação. A eficiência de encapsulamento da ovalbumina foi de aproximadamente 17%. A microscopia confocal mostrou claramente a associação entre ovalbumina e a cadeias de CMCS nas nanopartículas. Sugerimos, portanto, que tal sistema pode ser considerado como candidato atraente e promissor para o carreamento de proteínas e antígenos. O principal desafio que limita o uso desses carreadores consiste na instabilidade em meio aquoso. Assim, o próximo passo deste trabalho foi determinar a robustez de várias formulações utilizandose diferentes protocolos de liofilização. Este estudo demonstrou que o manitol em uma concentração de 10% (p/v) é adequado para preservar da agregação as nanocápsulas de CMCS carregadas com ovalbumina durante a liofilização e subsequente reconstituição. Mais importante, os resultados mostraram que uma etapa de annealing tem um enorme impacto sobre a porosidade da amostra liofilizada devido a quase completa cristalização do manitol, uma vez que a matriz cristalina evita o colapso parcial e a formação de poros maiores observados na ausência do annealing. Portanto, a observação comum de que o annealing aumenta o tamanho doporos devido ao crescimento dos cristais de gelo nem sempre se aplica, pelo menos quando a cristalização de um soluto está envolvida. Uma vez que todas as caracterizações e estudos de estabilidade foram realizados, o principal objetivo deste estudo foi desenvolver um sistema estável de delivery de antígeno para imunização oral utilizando CMCS e vírus rábico inativado (RV) como antígeno. Verificou-se que as nanopartículas carregadas com RV aumentam as respostas imune sistêmica (IgG) e local (IgA) contra o RV após administração oral em camundongos. As doses efetivas 50% foram 50 vezes maiores que os controles negativos, indicando que a resposta imune foi iniciada apenas após a terceira dose da vacina. Além disso, foram produzidos anticorpos neutralizantes suficientes para proteção contra os efeitos nocivos do vírus rábico. Conclui-se, portanto, que as nanopartículas de CMCS formuladas neste estudo, são adequadas para o delivery oral de vacinas, e podem ser sugeridas como um sistema promissor de delivery para uma gama diversa de antígenos, bem como para o delivery de genes/proteínas, especialmente para aqueles carregados positivamente. Uma vez que diversas abordagens mostram que uma intervenção efetiva em casos de inflamação alérgica de vias aéreas pode ser conseguida por meio de células secretoras de interleucina 10 (IL-10) mediante ativação por alergenos, a parte final deste trabalho esteve dedicada a avaliação de nanopartículas de quitosana carregadas com IL-10 (IL10-CSNPs) como possível ferramenta terapêutica inalável para prevenção de exacerbações em pacientes asmáticos. Como controles positivos, avaliou-se adicionalmente se as interleucinas 17A (IL-17A) e 9 (IL-9) possuem a capacidade de estimular a contratilidade de células humanas de músculo liso de vias aéreas humanas (HASM) por meio de citometria de torção magnética (MTC). Uma diminuição significativa da rigidez celular basal foi observada em células HASM pré-tratadas com IL-10, mas não com IL10-CSNPs, enquanto que o tratamento com IL-17A aumentou significativamente a magnitude rigidez celular basal. Nossos resultados revelam um mecanismo previamente desconhecido subjacente à imunoterapia para prevenção e tratamento da asma
Subject(s)
Asthma/pathology , In Vitro Techniques/instrumentation , Pharmaceutical Preparations , Ovalbumin/analysis , Chitosan/analysis , Administration, Oral , Interleukins/pharmacology , Microscopy, Confocal/methods , Nanocapsules , Nanoparticles/classification , Freeze Drying/methodsABSTRACT
@#Paclitaxel(PTX), an effective anti-tumor drugs, is water-insoluble. And Cremophor as a solubilizer in its commercial formulation, Taxol® , often causes side-effects which limit its antitumor effect. We designed and synthesized PEGylated carboxymethyl chitosan-rhein(CRmP)conjugate, and further prepared PTX-loaded CRmP polymeric micelles(PTX/CRmP). CRmP conjugate was characterized by fourier transform infrared spectrum(FT-IR)and nuclear magnetic resonance spectroscopy(1H NMR). The particle size and surface morphology of PTX/CRmP were characterized by dynamic laser particle size analyzer(DLS)and atomic force microscope(AFM), respectively. The cytotoxicity of CRmP conjugate and PTX/CRmP against MCF-7 cells were evaluated by MTT assay. The results showed that CRmP conjugates displayed very low cytotoxicity and that PTX/CRmP exhibited better in vitro anti-tumor activity than Taxol® at the same drug concentration after a long-term administration.
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Objective: To study the rat intestinal absorption characteristic of puerarin loaded O-carboxymethyl chitosan (CMCS) microspheres in situ. Methods: Single-pass intestinal perfusion (SPIP) model was used for rat in situ and HPLC to determine the concentration of puerarin. The effects of different perfusion rate, drug concentration, and intestinal segments on intestinal absorption were investigated, and the absorption characteristics of the puerarin and puerarin loaded O-CMCS microspheres were compared. Results: Perfusion rate had significant effect on the absorption rate constants (Ka) and the apparent absorption coefficient (Papp) (P 0.05); Ka and Papp of drug loaded microspheres in jejunum and ileum showed no significant difference, but they were significantly higher than that in duodenum (P < 0.05); The drug loaded microspheres and puerarin had the significant difference in Ka and Papp in jejunum (P < 0.05). Conclusion: The absorption mechanism of puerarin in the microspheres is passive diffusion, puerarin is absorbed well in jejunum and ileum, and puerarin loaded O-CMCS microspheres can significantly improve the absorption of puerarin.
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Objective To study the hemostasis activity of iodine complex with carboxymethyl chitosan .Methods The polymers were prepared with azodiisobutyronitrile as the initiating agent and sodium acrylate ,N‐vinylpyrrolidone ,carboxym‐ethyl chitosan and N ,N′‐methylene diacrylamide as the raw materials .It was then complexed with iodine to generate iodine complex with carboxymethyl chitosan ,and the hemostasis activity was tested at the same time .Results The polymers could absorb water with the value of 103g/g and showed potent hemostasis activity for auricular veins and femoral veins .Conclusion The results showed that hemostatic effect of polymers was better than that of hemostatic sponge and Quikclot .
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Objective To explore the changes of PH values of N,O-CMC/β-TCP compositive materials with different mass fractions in simulated body fluids (SBF)and their influence in the growth of MG63 cells, and to illustrate their mechanisms, and to provide reference for the further research on the bone repair materials. Methods The N,O-CMC/β-TCP with mass fractions of 2/1,1/1 and 1/2 were used as experimental groups,and the collagen nano calcium phosphate bone repair material as control group. The materials with different mass fractions were immersed in SBF and the pH values were measured by pH meter after soaking for 7,14,21 and 28d,respectively.The MG63 cells with the concentration of 1 × 105 mL-1 were inoculated and co-cultured in experimental and control groups,the adhesion and morphological changes of MG63 cells in each group were observed by scanning electron microscope and the cell proliferation was detected by MTT method after co-culturing for 2,4 and 6 d.Results The pH values were 6.70-7.25 in N,O-CMC/β-TCP (1/2)group and N,O-CMC/β-TCP (2/1)groups and the pH value in N,O-CMC/β-TCP (1/1)group was basically 7.15. The cells in N,O-CMC/β-TCP (2/1)group formed owe full,spreading face small and less secretion,but the cells in N,O-CMC/β-TCP 1/2 and 1/1 groups formed in full, pseudopodia interconnection, widely spreading and more secretions under electron microscope. The proliferation rate of the cells in N,O-CMC/β-TCP with (1/1 ) and N,O-CMC/β-TCP (2/1)groups had no statistical difference compared with control group (P>0.05),but there was significant difference between control group and N,O-CMC/β-TCP (1/2)group (P<0.05).Conclusion The changes of pH values of N,O-CMC/β-TCP materials with different mass fractions in SBF are small and the pH values are neutral;the order of the mass fraction of N,O-CMC/β-TCP to promote the growth of MG63 cells is 1/1,2/1,and 1/2.
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Objective To investigate the characteristics in vitro and hemostatic function of O -carboxymethyl chitosan multi-hemostatic sponge. Methods Freeze-drying technology was applied on preparation of O -carboxymethyl chitosan hemostatic sponge. The physicochemical properties of the self-produced multi-hemostatic sponge were observed for its appearance, porosity rate,water absorption,and density. The hemostatic effect was compared between the self-produced hemostatic sponge and commercially available absorbable gelatin sponge in rabbit models with ear venous and arterial injuries. Results The self-produced hemostatic sponge was off-white and full of pores with good tenacity and even net texture. Its porosity ratio, water absorption rate, and density were 67. 23%,38. 77%,and 0. 043 4 g·(cm3)-1,respectively. The bleeding time volume were significantly lower from the self-produced sponge than that from the commercially available gelatin sponge. No secondary re-bleeding was observed. Conclusion The self-produced O -carboxymethyl chitosan multi-hemostatic sponge displays stable physicochemical characteristics and reliable hemostatic effect.
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OBJECTIVE: To investigate the effects of O-carboxymethyl chitosan (O-CMC) multi-hemostatic sponge on the immobilization of thrombin. METHODS: The formulation of O-CMC multi-hemostatic sponge was optimized by using central composite design-response surface methodology (CCD-RSM), in which the O-CMC, glutaraldehyde and thrombin were used as enzyme immobilization carrier, crosslink agent and coagulant, respectively. The crosslinked conditions of thrombin were studied by determining the enzymatic activity yield. RESULTS: The optimized concentrations of O-CMC, thrombin and glutaraldehyde were 2.49%, 49.87 U · mL-1, 0.49%, respectively. CONCLUSION: O-CMC multi-hemostatic sponge has the positive immobilization effect on thrombin.
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Objective To observe the effect of intra-articular injection of CM-chitosan on nuclear factor κB (NF-κB) activation and nitric synthase expression in rat osteoarthritis cartilage,and to explore the mechanism of inhibition of joint destruction.Methods Thirty-six SD rats were randomly divided into three groups:A,B,C,12 in each group.Group A was the sham group,group B,C rats had the medial collateral ligaments cut off and part of medial meniscus were removed to establish osteoarthristis model.Group C rats were injected with 3％ carboxymethyl chitosan intra-articularly 0.15 mg/kg 5 weeks later,and then repeated injection every 1 week.Animals were sacrificed 11 weeks after surgery.The gross changes of cartilage and the expression of NF-κB (P65) were compared by immunohistochemistry,the protein expression of I-κB and P65 in nucleus were detected by Western-bloting.Inducible nitric oxide synthase (iNOS) mRNA and protein expres-sion were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and western blot.The general score of cartilage was analyzed by H test,the rest data was analyzed by one-way ANOVA.Results The cartilage degeneration scores pf group C (intra-articular injection of CM-chitosan group) were significantly less than those of group B.The protein expression of NF-κB of the articular cartilage in group C (106±7)was significantly lower than group B (147±8),the I-κB degradation was inhibited significantly in group C,and the expression of iNOS mRNA and iNOS protein were reduced in OA art~icular cartilage of arthritis rat chondrocytes,therefore,it had protective effect on articular cartilage.Conclusion CMC may inhibit NF-κB signaling pathway by inhibiting the degradation of I-κB in cartilage,which reduces iNOS mRNA and protein expression in rat osteoarthritis cartilage,thereby protects rat osteoarthritis cartilage cells.
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Objective: To evaluate the acute toxicity of carboxymethyl chitosan-2, 2’ ethylenedioxy bis-ethylamine-folate (CMC-EDBE-FA) and as well as possible effect on microbial growth and in vitro cell cyto-toxicity. Methods: CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2, 2’ ethylenedioxy bis-ethylamine. In vivo acute toxicity, in vitro cyto-toxicity and antimicrobial activity of CMC-EDBE-FA nanoparticle were determined. Results: Vancomycin exhibited the antibacterial activity against vancomycin sensitive Staphylococcus aureus, but CMC-EDBE-FA nanoparticle did not give any antibacterial activity as evidenced by minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), disc agar diffusion (DAD) and killing kinetic assay. Further, the CMC-EDBE-FA nanoparticle showed no signs of in vivo acute toxicity up to a dose level of 1000 mg/kg p.o., and as well as in vitro cyto-toxicity up to 250 μg/mL. Conclusions: These findings suggest that CMC-EDBE-FA nanoparticle is expected to be safe for biomedical applications.
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Objective: To evaluate the potency of carboxymethyl chitosan-2, 2’ ethylenedioxy bis-ethylamine-folate (CMC-EDBE-FA) on tissue injury, antioxidant status and glutathione system in tissue mitochondria and serum against nicotine-induced oxidative stress in mice. Methods:CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2, 2’ ethylenedioxy bis-ethylamine. Animals were divided into four groups, i.e., control, nicotine (1 mg/kg bw/day), CMC-EDBE-FA (1 mg/kg bw/day) and nicotine (1 mg/kg bw/day) and CMC-EDBE-FA (1 mg/kg bw/day) for 7 days. Levels of lipid peroxidation, oxidized glutathione level, antioxidant enzyme status and DNA damage were observed and compared. Results: The significantly increase of lipid peroxidation, oxidized glutathione levels and DNA damage was observed in nicotine treated group as compared with control group; those were significantly reduced in CMC-EDBE-FA supplemented group. Moreover, significantly reduced antioxidant status in nicotine treated group was effectively ameliorated by the supplementation of CMC-EDBE-FA. Only CMC-EDBE-FA treated groups showed no significant change as compared with control group; rather than it repairs the tissue damage of nicotine treated group. Conclusions: These findings suggest that CMC-EDBE-FA is non-toxic and ameliorates nicotine-induced toxicity.
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Objective Although chitosan has excellent biocompatibility and biodegradability, it is only soluble in acid solution that is not feasible for application in tissue engineering. The current study is aimed to prepare the carboxymethyl chitosan (CMC) for the purpose of improving the solubility of chitosan to meet the requirement of development of tissue engineering scaffolds. Methods The preparation methods and process conditions, such as the proportion of reactant, reaction temperature, reaction time and so on for three types of carboxymethyl chitosan were studied. Results The results indicated that optimal process conditions of three types of water soluble chitosan were obtained. Conclusion Water solubility of chitosan is greatly improved through carboxymethyl modification, which provides possibilities and foundation for further research.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the potency of carboxymethyl chitosan-2, 2' ethylenedioxy bis-ethylamine-folate (CMC-EDBE-FA) on tissue injury, antioxidant status and glutathione system in tissue mitochondria and serum against nicotine-induced oxidative stress in mice.</p><p><b>METHODS</b>CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2, 2' ethylenedioxy bis-ethylamine. Animals were divided into four groups, i.e., control, nicotine (1 mg/kg bw/day), CMC-EDBE-FA (1 mg/kg bw/day) and nicotine (1 mg/kg bw/day) and CMC-EDBE-FA (1 mg/kg bw/day) for 7 days. Levels of lipid peroxidation, oxidized glutathione level, antioxidant enzyme status and DNA damage were observed and compared.</p><p><b>RESULTS</b>The significantly increase of lipid peroxidation, oxidized glutathione levels and DNA damage was observed in nicotine treated group as compared with control group; those were significantly reduced in CMC-EDBE-FA supplemented group. Moreover, significantly reduced antioxidant status in nicotine treated group was effectively ameliorated by the supplementation of CMC-EDBE-FA. Only CMC-EDBE-FA treated groups showed no significant change as compared with control group; rather than it repairs the tissue damage of nicotine treated group.</p><p><b>CONCLUSIONS</b>These findings suggest that CMC-EDBE-FA is non-toxic and ameliorates nicotine-induced toxicity.</p>