Biomedical Materials
·
2014
·Vol. 9
·期 1
·015007
·
IF 2.922
Qi Wang,Pei Liu,Peifeng Liu,Tao Gong,Suming Li,Yourong Duan,Zhirong Zhang
Biodegradable chitosan-graft-polylactide (PLA–CS) copolymers were prepared by the grafting of a poly(L-lactide) (PLLA) or poly(D-lactide) (PDLA) precursor to the backbone of chitosan using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC ⋅ HCl) and N-hydroxysuccinimide (NHS) as a coupling agent. The blood and cell compatibility of the graft copolymers were investigated in comparison to PLLA and PDLA homopolymers. The coagulation properties of PLA–CS were evaluated by hemolysis, plasma recalcification, dynamic blood clotting and protein absorption assays. PLA–CS copolymers present similar hemolysis ratio and plasma recalcification time as PLA, but slower dynamic blood clotting and lower protein absorption. The cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), agar diffusion and lactate dehydrogenase (LDH) experiments. All the samples presented no effect on the viability to cells. Inflammatory cytokine analysis using sandwich ELISAs revealed that PLA–CS would not stimulate inflammatory activity.
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MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
Yuanyuan Guo,Min Chu,Songwei Tan,Shuang Zhao,Hanxiao Liu,Ben Oketch Otieno,Xiangliang Yang,Chuanrui Xu,Zhiping Zhang
To overcome the P-glycoprotein (P-gp)-induced multidrug resistance (MDR) of cancer cells, a novel copolymer, chitosan-graft-d-α-tocopheryl polyethylene glycol 1000 (TPGS) (CT) was synthesized for doxorubicin (DOX) delivery by the P-gp inhibiting virtue of TPGS. DOX-loaded CT nanoparticles (NPs) were fabricated by a modified solvent extraction/evaporation method combined with ionic cross-linking to form a uniform particle size of 140–180 nm with ∼40% DOX loading efficiency. These drug-loaded CT NPs demonstrated a pH-responsive release behavior, and DOX was released more quickly under low pH values. Significant cell cytotoxicity was observed on the human hepatocarcinoma cells (HepG2 and BEL-7402) and human breast adenocarcinoma cells (MCF-7). The cell cytotoxicity and apoptosis of drug-resistant cells (MCF-7/DOX and BEL-7402/5-Fu), was greatly enhanced as compared to Adriamycin. The IC50 value showed that DOX-loaded CT NPs could be 1.5–199-fold more effective than Adriamycin. This can be attributed to the P-gp blocking and down-regulation of ATP levels by the CT NPs. The potential of these NPs to act as an oral delivery system was also investigated. Both the pharmacokinetic properties and in vivo antitumor activity of DOX-loaded CT NPs were improved compared with Adriamycin.
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RSC Advances
·
2015
·Vol. 5
·期 110
·90969-90975
·
IF 3.84
Jian Li,Yanqing Xu,Mengqing Hu,Jiangnan Shen,Congjie Gao,Bart van der Bruggen
The application of electrodialysis (ED) for desalination requires the use of natural seawater or river water, in which the presence of multivalent ions is inevitable. This currently limits the process performance. Membranes with selectivity for monovalent ions may overcome this limitation. This study used the method of electro-deposition with chitosan/aniline polymer as a modification material to coat a commercial anion exchange membrane in view of obtaining selectivity for monovalent ions. Chitosan was grafted with polyaniline through copolymerization using ammonium persulfate as an initiator. FTIR spectra of the composites revealed that there was a strong interaction between substituted polyanilines and chitosan. The method was used to prepare a series of membranes by varying the aniline ratio and polymerization time. The chemical composition and surface properties of the membranes were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), respectively. Current–voltage curves and resistance were measured to characterize the transport properties of the membranes and the membrane conductivity. The results show that the membrane conductivity increases with the aniline ratio; the selectivity initially increases with the aniline ratio, and then decreases again. The optimum modification condition was an electrodeposition time of 4 h with an aniline ratio of 0.4. Using the modified membrane in concentrated sea water, it was demonstrated that the modified membrane has an excellent selectivity towards monovalent cations.
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JOURNAL OF APPLIED POLYMER SCIENCE
·
2015
·Vol. 132
·期 37
·
IF 1.768
Hongqiu Wei,Fenghua Zhang,Dawei Zhang,Yanju Liu,Jinsong Leng
With aim of constructing a class of functional environmentally friendly materials, we electrospun chitosan (CS) blends with various contents of poly(ethylene oxide) (PEO) into a series of composite nanofibrous membranes exhibiting shape-memory behaviors. In the present composite system, CS and PEO served as hard and soft domains, respectively. The CS, presenting no thermal transition, and the PEO, with apparent melting–crystallization, were demonstrated by differential scanning calorimetry testing. Characterizations also revealed that the morphologies of the CS/PEO membranes were controlled by the mass ratios of CS/PEO. The composite fibrous membranes showed great mechanical performances and thermal stabilities as well. Moreover, CS/PEO possessed excellent shape-memory behaviors. Such fibrous membranes could complete their shape-recovery processes within 20 s at the temperature of 20°C above the melting transition temperature ( T m ). Both the shape fixity and shape-recovery ratios were higher than 90%, even after five cycles. The CS/PEO fibrous membranes present significant potential applications in the field of biotechnology and tissue engineering, such as in scaffolds and smart tubes. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 42532.
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RSC Advances
·
2015
·Vol. 5
·期 38
·30303-30309
·
IF 3.84
Yangling Li,Ying Tan,Kun Xu,Cuige Lu,Xuechen Liang,Pixin Wang
An in situ hydrogel based on oxidation cholesterol starch (OCS) and O-carboxymethyl chitosan (CMCT) that is completely devoid of potentially cytotoxic small molecule cross-linkers and does not require complex manoeuvres or catalysis has been formulated and characterized. The network structure was created by Schiff base formation. The mechanical properties, internal morphology and swelling ability of the injectable hydrogel were examined. Rheological measurements demonstrated that increasing the concentration of the monomer improved the storage modulus. SEM showed that the hydrogel possessed a well-defined porous structure. In addition, the Schiff base reaction was acid sensitive. Under acid conditions, the hydrogel could hydrolyse quickly compared with high pH conditions. Doxorubicin (DOX) was used as a model drug to investigate the control and release properties of the hydrogel. The cytotoxic potential of the hydrogel was determined using an in vitro viability assay with L929 cells as a model and the results revealed that the hydrogel was non-cytotoxic.
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Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 45
·8884-8891
·
IF 4.726
Xiaoman Li,Bing Han,Xiaoyan Wang,Xuejun Gao,Fuxin Liang,Xiaozhong Qu,Zhenzhong Yang
The treatment of apical periodontitis (AP) remains challenging because traditional root canal therapy (RCT) outcomes are limited by the complexity of the root canal system, drug toxicity, and host immune factors. It is necessary to develop methods to prepare controlled drug release vehicles with improved biocompatibility for treatment of AP. Herein, calcium hydroxide microcapsules with chitosan and ethylcellulose coated (CS–EC@Ca(OH)2 microcapsules) were prepared and the presence of hydrogen bonding between shell materials was observed by FT-IR. Through release assessment and biological assays, we showed that the microcapsules had enhanced controlled-release performance and biocompatibility. In particular, drug release from the microcapsules was pH-triggered. The cumulative release of drugs in pH 5.0 buffer was 8-fold higher than that in pH 7.0 buffer. Furthermore, the microcapsules exhibited prolonged antibacterial activity against refractory strains of Enterococcus faecalis. Additionally, the CS–EC@Ca(OH)2 microcapsules reduced inflammation and promoted osteogenesis, which could be beneficial for the healing of AP with bone defects. Therefore, CS–EC@Ca(OH)2 microcapsules improve the innate properties of Ca(OH)2 and hold potential for AP treatment.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2014
·
IF 3.096
Rui Zhao,Xiang Li,Bolun Sun,Ying Zhang,Dawei Zhang,Zhaohui Tang,Xuesi Chen,Ce Wang
Chitosan and sericin are natural and low cost biomaterials. Both biomaterials displayed good compatibility to human tissues and antibacterial properties for biomedical application. In this study, we have successfully fabricated chitosan/sericin composite nanofibers by electrospinning. The obtained composite nanofibers were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectrometer (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) studies. The composite nanofibers had good morphology with diameter between 240 nm and 380 nm. In vitro methyl thiazolyl tetrazolium (MTT) assays demonstrated that the chitosan/sericin composite nanofibers were biocompatible and could promote the cell proliferation . Furthermore, the composite nanofibers showed good bactericidal activity against both of Gram-positive and Gram-negative bacteria. Thus, the chitosan/sericin composite nanofibers are promising for wound dressing applications.
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VACCINE
·
2014
·
IF 3.485
Qingfeng Liu,Chi Zhang,Xiaoyao Zheng,Xiayan Shao,Xi Zhang,Qizhi Zhang,Xinguo Jiang
The frequent outbreak of respiratory infectious diseases such as influenza and pulmonary tuberculosis calls for new immunization strategies with high effectiveness. Nasal immunization is one of the most potential methods to prevent the diseases infected through the respiratory tract. In this study, we designed a water-soluble system based on antigen/ N -trimethylaminoethylmethacrylate chitosan conjugates for nasal immunization. N -trimethylaminoethylmethacrylate chitosan (TMC) was synthesized by free radical polymerization of chitosan and N -trimethylaminoethylmethacrylate chloride and identified by 1 H NMR and FT-IR. Thiolated ovalbumin (OVA) was covalently conjugated to maleimide modified TMC with high conjugation efficiency. OVA conjugated TMC (OVA–TMC) significantly increased uptake of OVA by Raw 264.7 cells, which was 2.38 times higher than that of OVA/TMC physical mixture (OVA + TMC) at 4 h. After nasal administration, OVA–TMC showed higher transport efficiency to superficial and deep cervical lymph nodes than OVA + TMC or OVA alone. Balb/ C mice were intranasally given with OVA–TMC three times at 2-week internals to evaluate the immunological effect. The serum IgG, IgG1 and IgG2a levels of the OVA–TMC group were 17.9–87.9 times higher than that of the OVA + TMC group and comparable to that of the intramuscular group. The secretory IgA levels in nasal wash and saliva of the OVA–TMC group were 5.2–7.1 times higher than that of the OVA + TMC group while the secretory IgA levels of the intramuscular alum-precipitated OVA group were not increased. After immunofluorescence staining of nasal cavity, IgA antibody secreting cells were mainly observed in the lamina propria regions and glands of nasal mucosa. OVA–TMC showed little toxicity to the nasal epithelia or cilia of rats after nasal administration for three consecutive days. These results demonstrated that antigen conjugated TMC can induce both systemic and mucosal immune responses after nasal administration and may serve as a convenient, safe and effective vaccine for preventing respiratory infectious diseases.
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JOURNAL OF NANOPARTICLE RESEARCH
·
2013
·Vol. 15
·期 12
·1-15
·
IF 2.175
Huang Shengtang,Wan Ying,Wang Zheng,Wu Jiliang
Chitosan was conjugated with folic acid (FA) and the resulting chitosan derivatives with a FA-substitution degree of around 6 % was used to synthesize FA-conjugated chitosan–polylactide (FA–CH–PLA) copolymers to build a drug carrier with active targeting characteristics for the anticancer drug of paclitaxel (PTX). Selected FA–CH–PLAs with various polylactide percentages of about 40 wt% or lower were employed to fabricate nanoparticles using sodium tripolyphosphate as a crosslinker, and different types of nanoparticles were endued with similar average particle-sizes located in a range between 100 and 200 nm. Certain types of PTX-loaded FA–CH–PLA nanoparticles having encapsulation efficiency of around 90 % and initial load of about 12 % were able to release PTX in a controlled manner with significant regulation by polylactide content in FA–CH–PLAs. Targeting characteristic of achieved nanoparticles was confirmed using FA-receptor-expressed MCF-7 breast cancer cells. The uptake of PTX revealed that optimized FA–CH–PLA nanoparticles with an equivalent PTX-dose of around 1 μg/mL could have more than sixfold increasing abilities to facilitate intracellular paclitaxel accumulation in MCF-7 cells after 24 h treatment as compared to free PTX. At a relatively safe equivalent PTX-dose for normal MCF-10A mammary epithelial cells, the obtained results from Hoechst 33342 staining indicated that optimized PTX-loaded FA–CH–PLA nanoparticles had more than threefold increasing abilities to induce MCF-7 cell apoptosis in comparison to free PTX.
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Soft Matter
·
2013
·Vol. 9
·期 46
·11136-11142
·
IF 3.909
Jingjun Wu,Qian Zhao,Chengzhen Liang,Tao Xie
Enzyme-degradable hydrogels with aligned pores were prepared via unidirectional freezing of a mixed solution of oxidized dextran (oxDex) and chitosan (CHI) followed by cryo-gelation. At the frozen state, imine bonds as the crosslinking points of the hydrogels were formed as a result of the reaction between the aldehyde groups on the oxDex and the amino groups on the CHI. The morphologies of the obtained hydrogels were studied by confocal laser scanning microscopy (CLSM). Microtubular pores aligned along the freezing direction were obtained in the swollen state of the hydrogels. The pore size was adjustable ranging from 20 to 100 μm by controlling the freezing temperature in the unidirectional freezing step. Upon exposure of the hydrogels to chitosanase solution, chitosan can be hydrolyzed into short oligosaccharide fragments leading to collapse and degradation of the gel network. The degradation rate can be tuned by adjusting the gel composition and enzyme concentration.
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PLoS One
·
2015
·Vol. 10
·期 4
·e0121817
·
IF 3.234
Huiying Chen,Shaohui Cui,Yinan Zhao,Chuanmin Zhang,Shubiao Zhang,Xiaojun Peng
Modifying chitosan (CS) with polyethylenimine (PEI) grafts is an effective way to improve its gene transfection performance. However, it is still a challenge to conduct the grafting with fine control and high efficiency, particularly for the modification of water-insoluble CS. Herein, a novel method to graft CS with PEI (1.8 kDa, PEI-1.8) was developed by using ionic liquid 1-butyl-3-methyl imidazolium acetate ([BMIM]Ac) as a reaction solvent, water-insoluble CS as a reaction substrate and 1,1-carbonyldiimidazole (CDI) as a linking agent. The grafting reaction was greatly accelerated and the reaction time was largely shortened to 4 h by taking advantages of the good solubility of CS, the enhanced nucleophilicity of amino groups and the preferential stability of the activated complexes in the ionic liquid. The chitosan- graft -polyethylenimine (CS- g -PEI) products were characterized by 1 H NMR, FTIR and GPC. PEI-1.8 was quantitatively grafted to CS through urea linkages, and the grafting degree (GD) was conveniently tuned by varying the molar ratios of PEI-1.8 to D-glucosamine units of CS in the range of 9.0 × 10 -3 to 9.0 × 10 -2 . Compared with CS, the synthesized CS- g -PEI copolymers showed higher pDNA-binding affinity, which increased with the GD as shown in Agarose gel electrophoresis. The dynamic light scattering (DLS) experiment demonstrated that the CS- g -PEI/pDNA polyplexes had suitable particle sizes and proper ζ-potentials for cell transfection. The CS- g -PEI copolymer with a medium GD of 4.5% conferred the best gene transfection, with the efficiency 44 times of CS and 38 times of PEI-1.8 in HEp-2 cells. The cytotoxicity of CS- g -PEI was tested and found nearly as low as that of CS and much lower than that of PEI.
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JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION
·
2013
·Vol. 28
·期 3
·617-621
·
IF 0.484
Zeng Rong,Wang Zehu,Wang Hongran,Chen Liqiang,Qiao Renzhong,Hu Liming,Li Zelin
Chitosan-stavudine (d4T) conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitosan-5′- O -succinyl-d4T conjugate was crosslinked with sodium tripolyphosphate (TPP) to obtain the chitosan-d4T conjugate nano-prodrug. The morphologies of chitosan-d4T conjugate nanoparticles were observed by transmission electron microscopy (TEM), and their zeta potential, particle size, and polydispersity (size distribution) were measured by the dynamic light scattering (DLS) techniques. In vitro drug release studies at pH 1.1 and pH 7.4 indicate that the crosslinked chitosan-d4T conjugate nano-prodrug can prevent the coupled d4T from leaking out before entering the target viral reservoirs and provide a mild sustained release without the burst release. The results reveal that constructing conjugated chitosan nano-prodrugs may be a promising approach for improving the therapy efficacy of drugs in antiviral treatment.
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