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Chitosan
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2021 · IF 6.953

Chitosan modified squalene nanostructured lipid carriers as a promising adjuvant for freeze-dried ovalbumin vaccine

Xiuge Gao,Jiahao Gong,Ying Cai,Jiacai Wang,Jia Wen,Lin Peng,Hui Ji,Shanxiang Jiang,Dawei Guo

As immune adjuvants assisting vaccines, nanoparticle delivery systems have been widely exploited. Squalene, the major ingredient of approved adjuvant MF59, has great potential in activating immune responses. In the current study, model antigen ovalbumin (OVA) was encapsulated into squalene-based nanostructured lipid carriers (NLCs), and the chitosan, a cationic polysaccharide, was used for modifying nanoparticles to develop a functionalized and cationic nanoparticle delivery system (OVA-csNLCs). Firstly, the optimal formulation of csNLCs was successfully screened out, and had hydrodynamic diameter of 235.80 ± 5.99 nm and zeta potential of 34.90 ± 6.95 mV. Then, the generated OVA-csNLCs had no significant difference in hydrodynamic diameter and exhibited lower zeta potential of 19.03 ± 0.31 mV and high encapsulation efficiency of 83.4%. Sucrose (10%, w /w) was selected as optimal lyoprotectant, exhibiting good stability of OVA-csNLCs in the form of freeze-dried powder. More importantly, the OVA-csNLCs effectively promoted OVA antigen uptake by macrophage, significantly enhanced the level of OVA-specific IgG, and induced a Th2-based immune response in vivo. Furthermore, mice immunization experiment demonstrated that OVA-csNLCs had well biocompatibility and facilitated spleen lymphocytes proliferation. Above findings indicate that chitosan modified squalene nanostructured lipid carriers show promise as antigen delivery system and an open adjuvant platform.

✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2022 · IF 8.025

Carboxymethyl chitosan-based multifunctional hydrogels incorporated with photothermal therapy against drug-resistant bacterial wound infection

Peng Jiang,Lijie Huang,Junjie Wang,Qiulei Li,Haibo Mu

Wound infection especially that induced by drug resistant bacteria has been considered an increasing medical crisis. Herein a biocompatible wound dressing is conveniently constructed by incorporating (Sr 0.6 Bi 0.305 ) 2 Bi 2 O 7 (denoted as SBO) with excellent photothermal performance into a facile antibacterial hydrogel (gel) obtained from multiple physical crosslinks among Ag + , carboxymethyl chitosan and polyacrylic acid. The prepared SBO gel features excellent bactericidal activities, hemostasis, adequate mechanical properties, adhesiveness and adsorption capacities to bacterial cells and toxin. The gel can disperse SBO homogeneously in the network and SBO effectively convert visible light energy into localized heat for synergistic sterilization. In vitro assays confirm the potent broad-spectrum bactericidal activities of SBO gel to some common pathogens and drug resistant strains such as MRSA and CAPA. Mice model of MRSA-induced wound infections verified the practical efficacy of SBO gel in combating bacterial infections and accelerating wound healing. Moreover, this is the first report of SBO as a photothermal agent applied in anti-infection treatment. All of these results highlight the potential application of SBO gel in drug-resistant bacteria associated wound management.

✓ 已验证 DOI PubMed 高影响因子
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Nanomaterials · 2022 ·Vol. 12 ·期 17 ·2933 · IF 5.719

Electrospun Chitosan–Polyvinyl Alcohol Nanofiber Dressings Loaded with Bioactive Ursolic Acid Promoting Diabetic Wound Healing

Hongyu Lv,Meng Zhao,Yiran Li,Kun Li,Shaojuan Chen,Wenwen Zhao,Shaohua Wu,Yantao Han

The design and development of novel dressing materials are urgently required for the treatment of chronic wounds caused by diabetic ulcers in clinics. In this study, ursolic acid (UA) extracted from Chinese herbal plants was encapsulated into electrospun nanofibers made from a blend of chitosan (CS) and polyvinyl alcohol (PVA) to generate innovative CS-PVA-UA dressings for diabetic wound treatment. The as-prepared CS-PVA-UA nanofiber mats exhibited randomly aligned fiber morphology with the mean fiber diameters in the range of 100–200 nm, possessing great morphological resemblance to the collagen fibrils which exist in the native skin extracellular matrix (ECM). In addition, the CS-PVA-UA nanofiber mats were found to possess good surface hydrophilicity and wettability, and sustained UA release behavior. The in vitro biological tests showed that the high concentration of UA could lead to slight cytotoxicity. It was also found that the CS-PVA-UA nanofiber dressings could significantly reduce the M1 phenotypic transition of macrophages that was even stimulated by lipopolysaccharide (LPS) and could effectively restore the M2 polarization of macrophages to shorten the inflammatory period. Moreover, the appropriate introduction of UA into CS-PVA nanofibers decreased the release levels of TNF-α and IL-6 inflammatory factors, and suppressed oxidative stress responses by reducing the generation of reactive oxygen species (ROS) as well. The results from mouse hepatic hemorrhage displayed that CS-PVA-UA nanofiber dressing possessed excellent hemostatic performance. The in vivo animal experiments displayed that the CS-PVA-UA nanofiber dressing could improve the closure rate, and also promote the revascularization and re-epithelization, as well as the deposition and remodeling of collagen matrix and the regeneration of hair follicles for diabetic wounds. Specifically, the mean contraction rate of diabetic wounds using CS-PVA-UA nanofiber dressing could reach 99.8% after 18 days of treatment. In summary, our present study offers a promising nanofibrous dressing candidate with multiple biological functions, including anti-inflammation, antioxidation, pro-angiogenesis, and hemostasis functions, for the treatment of hard-to-heal diabetic wounds.Keywords:electrospinning;bioactive nanofibers;ursolic acid;wound dressing;diabetic wound

✓ 已验证 DOI PubMed 高影响因子
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International Journal of Polymer Science · 2017 · IF 1.077

Antibacterial Activity and Physical Properties of Fish Gelatin-Chitosan Edible Films Supplemented with D-Limonene

Yunzhen Yao,Ding Ding,Hongyuan Shao,Qifan Peng,Yaqin Huang

Fish gelatin-chitosan edible films with D-limonene were successfully prepared, which exhibited exceptional mechanical properties and antimicrobial activity. It has been demonstrated that water-soluble chitosan, fish gelatin, and D-limonene could be a candidate precursor to prepare low cost and high-performance edible food packaging material. The results showed that D-limonene in the films could effectively resist the penetration of light and water because of its hydrophobicity. Moreover, the elongation at break (EAB) increased with the addition of D-limonene, which indicated that D-limonene served as a strong plasticizer for the film. Microscopic characterization showed that D-limonene was uniformly distributed in the as-prepared film. And we found that the film exhibited strong antibacterial activity against Escherichia coli (E. coli). All the results indicate that the as-prepared film could be a promising food packaging.

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CARBOHYDRATE POLYMERS · 2018 · IF 5.158

Biomimetic mineralization of carboxymethyl chitosan nanofibers with improved osteogenic activity in vitro and in vivo

Xiujuan Zhao,Liangyu Zhou,Qingtao Li,Qingxia Zou,Chang Du

Inspired by the natural extracellular matrix, the organic-inorganic composite nanofibers are promising scaffolds for bone tissue engineering. Chitosan-based nanofibers are widely used as bone tissue engineering scaffolds with good biocompatibility but pungent solvents are frequently used for its processing. Carboxymethyl chitosan (CMCS), a water-soluble derivative of chitosan, has better biodegradability and bioactivity which allows CMCS to chelate Ca 2+ and induce the deposition of apatite. Moreover, with water as solvent, CMCS nanofibers avoid the acidic salt removal comparing to electrospun-chitosan. In this study, we successfully prepared uniform CMCS nanofibers with the aid of polyethylene oxide (PEO) and obtained the optimized conditions with a voltage of 25 kV and PEO of molecular weight 1000 kDa. We further prepared hydroxyapatite (HA) coated electrospun CMCS nanofibers by biomimetic mineralization using 5 times simulated body fluid. The promotion of osteogenic differentiation of mouse bone marrow stromal cells (mBMSCs) in vitro was evaluated on the nanofibers scaffolds. Cell experiments revealed that CMCS-HA composite nanofibers increased the ALP activity. The gene expression level of Runx2 and ALP were about 1.6 and 4.3 folds at the 7 days, and 5.1 and 10 folds at the 14 days on CMCS-HA nanofibrous membranes than that on CMCS alone samples. The level of OCN increased by 24 and 1.5 times on the CMCS-HA scaffolds than CMCS scaffolds at the 14 and 21 days. In vivo new bone formation by nanofiber scaffolds was investigated in a critical-size rat calvarial bone defect model. Micro-CT results showed that the whole defect was covered by new bone after CMCS-HA filling the defect for 12 weeks. The results of H&E staining and Masson’s trichrome staining on histological sections further confirmed that composite nanofibers promoted new bone formation and maturation.

✓ 已验证 DOI PubMed 高影响因子
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International Journal of Nanomedicine · 2023 · IF 8

Chitosan Nanoparticles Strengthen Vγ9Vδ2 T-Cell Cytotoxicity Through Upregulation Of Killing Molecules And Cytoskeleton Polarization

Li Lin,Junyi He,Jiawei Li,Yan Xu,Jingxia Li,Yangzhe Wu

Background During the past few years, immune cell therapy for malignant cancer has benefited a considerable amount of patients worldwide. As one of several promising candidates for immunotherapy, Vγ9Vδ2 γδ T cells have many unique biological advantages, such as non-MHC restriction and have been noted as the earliest source of IFN-γ. However, potentiating anti-tumor functions of γδ T cells has become of particular interest to researchers studying γδ T cell applications.Purpose In this study, we proposed a nanotechnology-based methodology for strengthening γδ T cell functions.Methods As a type of reliable, biocompatible material, chitosan nanoparticles (CSNPs) were used to enhance anti-tumor immunity of γδ T cells.Results First, we found that the size of prepared CSNPs distributed 50 to 100 nm, and that CSNPs had optimal immunocompatibility. Then, we observed that CSNPs could induce α-tubulin cytoskeleton polarization and rearrangement, correlating with a higher killing ability of γδ T cells. Furthermore, we revealed that CSNPs could enhance Vγ9Vδ2 T cell anti-tumor functions by upregulating killing of related receptors, including NKG2D, CD56, FasL, and perforin secretion.Conclusion Our work provided evidence of application for CSNPs based bio-carrier in immunotherapy. More importantly, we proposed a new strategy for enhancing γδ T cell anti-tumor activity using nanobiomaterial, which could benefit future clinical applications of γδ T cells.

✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2021 · IF 6.953

Dual cure (thermal/photo) composite hydrogel derived from chitosan/collagen for in situ 3D bioprinting

Yidan Liu,Xin Luo,Wei Wu,Andi Zhang,Bingchuan Lu,Ting Zhang,Ming Kong

In situ 3D printing technologies is a new frontier for highly personalized medicine, which requires suitable bioink with rheology, biocompatibility, and gelation kinetics to support the right shape and mechanical properties of the printed construct. To this end, a facile design of thermo/photo dual cure composite hydrogel was proposed using MHBC and soluble collagen in this study. M/C composite hydrogel exhibited rapid thermo-induced sol-gel transition and contraction, tunable mechanical properties, proper microstructure and biodegradability for 3D cell culture, as well as improve cyto-compatibility, all of which were dependent upon the methacrylation degree of MHBC and M/C ratios. The printability of the optimal formulation (3% MHBC/1% collagen) was validated by its mild printing condition, rapid gelation of bioink at 37 °C and simple postprocessing manipulation. Both desirable printability and cyto-compatibility enable M/C composite hydrogel a potential candidate as bioink to be applied for in situ 3D bioprinting.

✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2020 ·Vol. 21 ·期 5 ·1635 · IF 4.556

Enhancing the Thermo-Stability and Anti-Bacterium Activity of Lysozyme by Immobilization on Chitosan Nanoparticles

Yanan Wang,Shangyong Li,Mengfei Jin,Qi Han,Songshen Liu,Xuehong Chen,Yantao Han

The recent emergence of antibiotic-resistant bacteria requires the development of new antibiotics or new agents capable of enhancing antibiotic activity. Lysozyme degrades bacterial cell wall without involving antibiotic resistance and has become a new antibacterial strategy. However, direct use of native, active proteins in clinical settings is not practical as it is fragile under various conditions. In this study, lysozyme was integrated into chitosan nanoparticles (CS-NPs) by the ionic gelation technique to obtain lysozyme immobilized chitosan nanoparticles (Lys-CS-NPs) and then characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), which showed a small particle size (243.1 ± 2.1 nm) and positive zeta potential (22.8 ± 0.2 mV). The immobilization significantly enhanced the thermal stability and reusability of lysozyme. In addition, compared with free lysozyme, Lys-CS-NPs exhibited superb antibacterial properties according to the results of killing kinetics in vitro and measurement of the minimum inhibitory concentration (MIC) of CS-NPs and Lys-CS-NPs againstPseudomonas aeruginosa(P. aeruginosa),Klebsiella pneumoniae(K. pneumoniae),Escherichia coli(E. coli), andStaphylococcus aureus(S. aureus). These results suggest that the integration of lysozyme into CS-NPs will create opportunities for the further potential applications of lysozyme as an anti-bacterium agent.Keywords:immobilization;chitosan nanoparticles;lysozyme;anti-bacterium activity

✓ 已验证 DOI PubMed 高影响因子
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Nano Research · 2018 ·Vol. 11 ·期 8 ·4278-4292 · IF 7.994

Convenient preparation of charge-adaptive chitosan nanomedicines for extended blood circulation and accelerated endosomal escape

Zhang Yapei,Li Yingying,Ma Jinlong,Wang Xinyu,Yuan Zhi,Wang Wei

A major impediment in the development of chitosan nanoparticles (CTS NPs) as effective drug delivery vesicles is their rapid clearance from blood and endosome entrapment. To overcome these problems, a convenient and promising template system was developed by decorating poly(methacrylic acid) (PMAA) to the surface of 10-hydroxy camptothecin (HCPT)-loaded CTS NPs (HCPT-CTS/PMAA NPs). The results show that the presence of negatively charged PMAA significantly elongated the blood circulation time of HCPT-CTS NPs from 12 to 24 h, and reduced the blood clearance (Cl) from 30.57 to 6.72 mL/h in vivo . The calculated area under curve (AUC 0-24h ) and terminal elimination half-life ( t 1/2 ) of HCPT-CTS/PMAA NPs were 4.37-fold and 2.48-fold compared with those of HCPT-CTS NPs. Furthermore, the positively charged HCPT-CTS/PMAA NPs triggered by tumor acidic microenvironment (pH 6.5) result in a 453-fold higher cellular uptake than the negatively charged counterparts at pH 7.4. Additionally, HCPT-CTS/PMAA NPs have the ability to escape endosomal entrapment via “proton sponge effect” after incubation with HepG2 cells for 3 h at pH 6.5. Taken together, these findings open up a convenient, low-cost, but effective way to prepare HCPT-CTS/PMAA NPs as a candidate for developing vectors with enhanced long blood circulation and endosomal escape ability in future clinical experiments.

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2016 · IF 3.138

Preparation and properties of a novel thermo-sensitive hydrogel based on chitosan/hydroxypropyl methylcellulose/glycerol

Tao Wang,Liman Chen,Tingting Shen,Dayang Wu

Chitosan-based thermosensitive hydrogels are known as injectable in situ gelling thermosensitive polymer solutions which are suitable for biomaterials. In this study, a novel thermosensitive hydrogel gelling under physiological conditions was prepared using chitosan together with hydroxypropyl methylcellulose and glycerol. Hydroxypropyl methylcellulose is to facilitate the thermogelation through large amounts of hydrophobic interactions. Glycerol in heavy concentration destroys the polymer water sheaths promoting the formation of the hydrophobic regions, and lowering the phase transition temperature. The thermosensitive hydrogels showed a physiological pH ranging from 6.8 to 6.9 and gelation time within 15   min at 37   °C. The prepared hydrogels were characterized by FT-IR, XRD, SEM, and rheological studies, mechanical studies and contact angle studies. The properties of degradability, cytotoxicity and protein release behaviors of the hydrogels were investigated. The results indicate this thermosensitive hydrogel possess good fluidity, thermosensitivity and biodegradability, as well as low-cytotoxicity and controlled release, showing the potential use in biomedical applications.

✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2018 · IF 3.909

Effects of chitosan nanoparticles on seed germination and seedling growth of wheat (Triticum aestivum L.)

Ruixin Li,Jinxia He,Hongguo Xie,Wenxia Wang,Santosh Kumar Bose,Yeqing Sun,Jianen Hu,Heng Yin

To investigate the effect and mechanism of chitosan nanoparticles (CSNPs) on the germination and seedling growth of wheat ( Triticum aestivum L.), we conducted systematic research on the impact of different concentrations (1–100 μg/mL) of CSNPs and chitosan (CS). The result of energy-dispersive spectroscopy (EDS) and confocal laser scanning microscopy (CLSM) showed that adsorption of CSNPs on the surface of wheat seeds was higher than that of CS. CSNPs had growth promoting effect at a lower concentration (5 μg/mL) compared with CS (50 μg/mL). In addition, the application of 5 μg/mL CSNPs induced the auxin-related gene expression, accelerated indole-3-acetic acid (IAA) biosynthesis and transport, and reduced IAA oxidase activity resulting in the increase of IAA concentration in wheat shoots and roots. The results suggest that CSNPs have positive effect on seed germination and seedling growth of wheat at a lower concentration than CS due to higher adsorption on the surface of wheat seeds.

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MATERIALS LETTERS · 2012 · IF 2.307

Development and characterization of injectable chitosan-based hydrogels containing dexamethasone/rhBMP-2 loaded hydroxyapatite nanoparticles

Chang Gao,Yurong Cai,Xiangdong Kong,Guoxiang Han,Juming Yao

The injectable chitosan/β-glycerophosphate (CS/GP) hydrogels were prepared with dexamethasone (Dex)/recombinant human bone morphogenetic protein (rhBMP-2) loaded hydroxyapatite nanoparticles (nHAP). The obtained samples were characterized by TEM, SEM, XRD and nitrogen adsorption tests, and the effect of Dex and rhBMP-2 on the mesenchymal stem cells (MSCs) was evaluated. The results showed that nHAP could be dispersed homogeneously in the matrix of injectable CS/GP hydrogels and the combination of Dex and rhBMP-2 could promote the proliferation and osteoblastic differentiation of MSCs, indicating that the prepared injectable CS/GP hydrogels with Dex and rhBMP-2 loaded nHAP have great potential in different orthopedic regenerative applications.

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