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Oral drug delivery is considered the most preferred mode of treatment because of its high patient compliance and minimal invasiveness. However, the oral delivery of protein drug has been a difficult problem which restricts its application due to the unstable and inefficient penetration of protein in the gastrointestinal tract. In this study, a novel OCMC/SA nanohydrogel was prepared by using of O-carboxymethyl chitosan (OCMC) and sodium alginate (SA) to solve the problem. The OCMC/SA had a typical nanostructure, which was helpful to increase the specific surface area and enhanced the bioavailability of the drugs. OCMC/SA had a high drug loading capacity and realized passive drug targeting function by responding to the different pH value of the microenvironment. It could have a certain protective effect on drugs in strong acid circumstances, while its structure got loosed and effectively released drugs in intestinal circumstances. OCMC/SA could release the drug for12 h, and the released insulin could maintain high activity. OCMC/SA nanohydrogel showed promising results in type 1 diabetic rats, and its pharmacological bioavailability was 6.57 %. In conclusion, this study constructed a novel OCMC/SA nanohydrogel, which had a lot of exciting characteristics and provided a new strategy for oral drug delivery.

After vitrectomy, the ideal vitreous substitute should be implanted to maintain the normal function of the eye. However, the existing materials (such as silicone oil, air, perfluorocarbons, etc.) still have some shortcomings and cannot fully meet the clinical needs. In this study, thiolated hyaluronic acid (SH-HA) was prepared based on hyaluronic acid. The SH-HA hydrogel was formed by a simple transformation of the sulfhydryl group to the disulfide bond, which had high transparency, controllable swelling property, suitable mechanical strength, excellent biocompatibility and similar physical and chemical properties to natural vitreous. SH-HA hydrogel was filled into the eyes of experimental rabbits to replace their own vitreous after vitrectomy. During the 90 days follow-up period, SH-HA hydrogel showed excellent intraocular compatibility, maintained normal intraocular pressure (IOP), and no cataract, endophthalmitis, retinal detachment and other complications were observed. In general, SH-HA hydrogel has great potential as a vitreous substitute.

Herein, the thermosensitive hydroxypropyl chitin (HPCT) hydrogel was prepared and the chemical structures, microstructures, rheological properties and degradation in vitro were investigated. The HPCT hydrogel possessed satisfactory biocompatibility in mouse fibroblast cells and Sprague Dawley rats. On the other hand, N-acetylglucosamine (NAG) and carboxymethyl chitosan (CMCS) provided favorable capacity for promoting cell proliferation, delaying cell apoptosis, and facilitating the insulin secretion of rat pancreatic beta cells (RIN-m5F) in three-dimensional culture. Most importantly, the effects of HPCT/NAG and HPCT/CMCS thermosensitive hydrogels as RIN-m5F cells carriers were evaluated via injection into different areas of diabetic rats. Our results demonstrated that HPCT/NAG and HPCT/CMCS hydrogels loaded RIN-m5F cells could keep cells survival, maintain insulin secretion and reduce blood glucose for one week. Overall, the functional thermosensitive hydrogels based on HPCT were effective cell carriers for RIN-m5F cells and might provide novel strategy for the treatment of diabetes via cell engineering.

Herein, the dopamine (DA) was grafted with oxidized sodium alginate (OSA) via Schiff base reduction reaction, aiming to fabricate novel DA-grafted OSA (OSA-DA) hydrogels with enhanced biocompatibility and suitable adhesion for clinical applications. The chemical structures of OSA-DA were characterized via UV-Vis, FTIR and

Nanocarriers have emerged as a promising cancer drug delivery strategy. Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemotherapy. Vitamin E derivatives have many essential functions for drug delivery applications, such as biological components that are hydrophobic, stable, water-soluble enhancing compounds, and anticancer activity. In addition, vitamin E derivatives are also effective mitocan which can overcome multi-drug resistance by binding to P glycoproteins. Here, we developed a carboxymethyl chitosan/vitamin E succinate nano-micellar system (O-CMCTS-VES). The synthesized polymers were characterized by Fourier Transform IR, and 1H NMR spectra. The mean sizes of O-CMCTS-VES and DOX-loaded nanoparticles were around 177 nm and 208 nm. The drug loading contents were 6.1%, 13.0% and 10.6% with the weight ratio of DOX to O-CMCTS-VES corresponding 1:10, 2:10 and 3:10, and the corresponding EEs were 64.3%, 74.5% and 39.7%. Cytotoxicity test, hemolysis test and histocompatibility test showed that it had good biocompatibility in vitro and in vivo. Drug release experiments implied good pH sensitivity and sustained-release effect. The DOX/O-CMCTS-VES nanoparticles can be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate is up to 62.57%. In the in vivo study by using H22 cells implanted Balb/C mice, DOX/O-CMCTS-VES reduced the tumor volume and weight efficiently with a TIR of 35.58%. The newly developed polymeric micelles could successfully be utilized as a nanocarrier system for hydrophobic chemotherapeutic agents for the treatment of solid tumors., Graphical abstract Schematic diagram of the O-CMCTS-VESnanoparticles with EPReffect for anticancer therapy.Image 1, Highlights • A nano-micellar system (O-CMCTS-VES) constituted by carboxymethyl chitosan and vitamin E succinate was fabricated. • The micelles hold high cytocompatibility, hemocompatibility, tissue compatibility, and drug load contents. • Drug release experiments implied good pH sensitivity and sustained-release effect of O-CMCTS-VES. • O-CMCTS-VES loading DOX showed efficient anti-tumor effect in vitro and in vivo.

STAT3 plays a particularly important role in several cancer-related signal transduction pathways. Silencing STAT3 via RNA interference or small molecule inhibitors induces the apoptosis of tumor cells, thereby inhibiting the growth of the tumors. In this study, short-hairpin RNA sequences targeting the STAT3 genes were designed, synthesized, and then connected to pGPU6/GFP/Neo plasmids as the shRNA-expression vectors. The expression of STAT3-shRNA was analyzed by real-time PCR, western blotting, and cell apoptosis assay to study the growth and apoptosis of the cells. Then, the effect of STAT3 knockdown on the NCI-H1650 cells was studied in a tumor mouse model. The results revealed that, after an in vitro transfection, the proliferation of NCI-H1650 cells was inhibited, and the cells were induced to apoptosis. The mRNA and protein expression levels of STAT3 were downregulated in the STAT3-shRNA group. In vivo, the tumor mass and volume in the STAT3-shRNA group were significantly lower than in the other two groups. Both the in vivo and in vitro results demonstrated a long-period inhibiting effect on NSCLC, especially in vivo, when the tumor inhibition rate could reach 50% in the STAT3-shRNA group, which is an exciting outcome. Moreover, the study of the conjugation of STAT3-shRNA and chitosan-based vectors revealed that they could be combined steadily with good cytocompatibility and transfection efficiency. These results together provide convincing evidence for the application of STAT3-shRNA used in the treatment of non-small lung cancer, which could be a promoting prospect for the development of gene therapy.

In this study, a chitosan-based composite multichannel nerve conduit consisting of a warp-knitted chitosan scaffold and internally oriented N-succinyl-chitosan (NS-chitosan) fibers was applied to bridge a 10-mm nerve defect in rats. This study confirmed that an external pipeline with appropriate mechanical support was obtained by warp knitting techniques and that NS-chitosan fibers were not toxic to L-929 and PC-12 cells. These fibers degraded slowly for over 90 days and exerted sustained neuroprotective effects on peripheral nerves through their ability to drive cellular migration, promote survival, and block apoptosis of damaged Schwann cells through the Bcl-2/Bax/caspase-3 pathway. The multichannel chitosan/NS-chitosan conduit represented a histologically and functionally successful nerve reconstruction across a damaged 10-mm peripheral nerve model, showing regenerative efficacy equal to that of an autograft. The results demonstrated that the chitosan/NS-chitosan conduit with a warp-knitted tube construct and aligned inner fiber had good mechanical and bioactive properties for nerve repair.

Chemotherapy-induced intestinal mucositis (CIM) is a significant dose-limiting adverse reaction brought on by the cancer treatment. Multiple studies reported that reactive oxygen species (ROS) is rapidly produced during the initial stages of chemotherapy, when the drugs elicit direct damage to intestinal mucosal cells, which, in turn, results in necrosis, mitochondrial dysfunction, and ROS production. However, the mechanism behind the intestinal redox system-based induction of intestinal mucosal injury and necrosis of CIM is still undetermined. In this article, we summarized relevant information regarding the intestinal redox system, including the composition and regulation of redox enzymes, ROS generation, and its regulation in the intestine. We innovatively proposed the intestinal redox “Tai Chi” theory and revealed its significance in the pathogenesis of CIM. We also conducted an extensive review of the English language-based literatures involving oxidative stress (OS) and its involvement in the pathological mechanisms of CIM. From the date of inception till July 31, 2021, 51 related articles were selected. Based on our analysis of these articles, only five chemotherapeutic drugs, namely, MTX, 5-FU, cisplatin, CPT-11, and oxaliplatin were shown to trigger the ROS-based pathological mechanisms of CIM. We also discussed the redox system-mediated modulation of CIM pathogenesis via elaboration of the relationship between chemotherapeutic drugs and the redox system. It is our belief that this overview of the intestinal redox system and its role in CIM pathogenesis will greatly enhance research direction and improve CIM management in the future.

Although in a series of studies, arginine peptides had shown the ability to promote the targeting delivery efficacy, the relationship between the transfection efficiency and the length of the poly-l-arginine chain had seldom been reported. This study was aimed to explore whether the chain length of poly-l-arginine grafted on chitosan had a great significance on the transfection efficiency of entering the cells. Herein, arginine and arginine peptide modified chitosan were synthesized as gene vectors (CS-Arg and CS-5Arg) and then the chemical structures were characterized by using 1 H NMR. The CS-Arg and CS-5Arg were combined with plasmids by electrostatic interactions to form stable particles. The morphology features, Zeta potentials, and buffering capacity of the complex particles were analyzed. Afterward, the combination ability with DNA and the protection ability to DNase I were studied, and the gene transfection efficiency and cellular uptake were investigated in vitro. The results showed that the gene transfection efficiency of the chitosan was significantly enhanced by arginine-graft modification. However, there were no significant differences between the CS-Arg and the CS-5Arg. The molecular simulation results indicated that the guanidine groups of grafted arginine were shielded by chitosan molecule and the guanidine groups contributed little to the gene transfection efficiency. The results demonstrated that the increased chain length of grafted arginine had no significantly enhanced effect on the transfection efficiency, which could provide convincing evidence for the construction and application of arginine and chitosan derivatives as gene vectors, and could promote the development of gene delivery system.

Third-degree scald, causing serious tissue destruction with continuous pain, easily leads to microbial infections and delayed wound healing. Therefore, a multifunctional treatment is attractive for seriously damaged tissue. Herein, carboxymethyl chitosan-coordinated argentum (Ag-CMC) was synthesized via a complexation method, and then the Ag

Herein, hydroxypropyl chitosan azide (AZ-HPCTS) was synthesized and prepared as a hydrogel coating applied to a polypropylene mesh (PPM) through UV irradiation. This study confirmed the hypothesis that hydrogels with porous three-dimensional network structures exhibited excellent biocompatibility and biodegradability and adhered well to PPM. During the 180-day follow-up period, the AZ-HPCTS-coated PPM (AH-PPM) promoted wound healing by promoting the secretion of transforming growth factor-beta1 (TGF-beta1) in the acute reaction stage, which was reduced to a lower level at 30 d. The PPM exhibited a lower fibrin lysozyme activity based on the expression of tissue plasminogen activator (tPA) compared with that of AH-PPM (P 0.05). The intraperitoneal adhesion score of AH-PPM decreased to 2.4 at 180 d in contrast with PPM (P 0.01), which remained at a high level throughout the study. In conclusion, the AZ-HPCTS hydrogel is a potential coating for hernia patches that deserves further study in the biomaterial field.

This study was aimed at preparing O-carboxymethyl chitosan (CM-CTS) fabrics, and examining the wound healing effects on partial-thickness burn. The functional polysaccharides were produced from chitosan needle-punched nonwovens reacted with chloroacetic acid. Then the biocompatibility and biological functions were evaluated through fibroblast L-929 and SD rats. CM-CTS fabrics were obtained with elongation at break more than 42%, tensile strength reaching 0.65 N/mm

Novel polymer-drug conjugates (CNC) were prepared from carboxymethyl chitosan (CMCS) and norcantharidin (NCTD) via amidation reaction and characterized by FTIR and 1H NMR spectroscopy. The aim of this study was to elucidate the antitumor efficacy of CNC on gastric cancer and the possible underlying mechanisms. The CNC conjugates possessed significant inhibitory effects on the proliferation of SGC-7901 cells and suppressed the migration as well as tube formation of HUVECs. Besides, Hoechst 33258 staining and Annexin V-FITC/PI detection suggested that the conjugates were more effective in triggering apoptosis of SGC-7901 cells compared with free NCTD. Moreover, CNC remarkably reduced systemic toxicity and enhanced the antitumor efficacy in vivo with a tumor suppression rate of 59.57% against SGC-7901 gastric tumor in BALB/c nude mice. Further investigation about the underlying mechanisms indicated that CNC could upregulate expressions of TNF-α and Bax, and downregulate expressions of VEGF, Bcl-2, MMP-2 and MMP-9, thereby inhibiting tumor metastasis and inducing apoptosis in vivo. Overall, our results demonstrated that CNC might be a promising and feasible polymer therapeutics for gastrointestinal tumor therapy.

Chitosan as a natural bioactive biopolymer has been commonly employed in guidance conduit for repairing peripheral nerve injury, due to its excellent properties of low toxicity, antibacterial properties, high biocompatibility and biodegradability. In this study, chitin and CM-chitosan were prepared from pharmaceutical grade chitosan. Moreover, a novel composite chitosan-based nerve graft comprising microporous chitin-based conduit and internal CM-chitosan fiber was constructed and applied to bridge sciatic nerve across a 10-mm defect in SD rats. The chitin/CM-chitosan artificial nerve graft could promote the proliferation of rat Schwann cells (RSC96) with good cell biocompatibility. After implantation, the artificial nerve graft showed slow degradation. No apparent toxicity was observed, and tissue inflammation was very slight after implantation, indicating favorable bio-safety of the nerve graft. Furthermore, the chitin/CM-chitosan artificial nerve graft could effectively promote restoration of damaged neurons with similar effect compared to the autograft. In conclusion, the composite biodegradable chitin/CM-chitosan nerve grafts possessed favorable biocompatibility and good potential in repairing peripheral nervous injury.

Vitreous, an essential dioptric medium for the human eyes, must be filled with artificial materials once damaged. Carboxymethyl chitosan (CMCTS) is one of the most important water-soluble chitosan derivatives with improved biocompatibility and biodegradability. In this study, oxidized hyaluronic acid (OHA) was prepared as crosslinking reagent. CMCTS and OHA were used to develop a biocompatible, self-repairing and in-situ injectable hydrogel for vitreous substitutes. Results showed the hydrogel with controllable swelling properties, high transparency, acceptable cytocompatibility on mouse fibroblast L929 and histocompatibility in vivo. Furthermore, hydrogel was injected in-situ into the vitreous cavity after vitrectomy on New Zealand Rabbits, no significant and persistent adverse effects were observed during the 90-day follow-up period. In addition, the hydrogel maintained intraocular pressure of the operated eyes and the inherent position of the retina. Collectively, this injectable, biodegradable, nontoxic hydrogel possessed enormous potential to become a vitreous substitute material.

Highlights • Radiomics-based classifier agreed with radiologists for the classification of COVID-19. • Radiomics enables to quantify the CT variation with SARS-CoV-2 positivity & SARS-CoV-2 negativity. • The features identified by multi-classifier can interpret and generalise the CT signs of COVID-19., Purpose To investigate the efficacy of radiomics in diagnosing patients with coronavirus disease (COVID-19) and other types of viral pneumonia with clinical symptoms and CT signs similar to those of COVID-19. Methods Between 18 January 2020 and 20 May 2020, 110 SARS-CoV-2 positive and 108 SARS-CoV-2 negative patients were retrospectively recruited from three hospitals based on the inclusion criteria. Manual segmentation of pneumonia lesions on CT scans was performed by four radiologists. The latest version of Pyradiomics was used for feature extraction. Four classifiers (linear classifier, k-nearest neighbour, least absolute shrinkage and selection operator [LASSO], and random forest) were used to differentiate SARS-CoV-2 positive and SARS-CoV-2 negative patients. Comparison of the performance of the classifiers and radiologists was evaluated by ROC curve and Kappa score. Results We manually segmented 16,053 CT slices, comprising 32,625 pneumonia lesions, from the CT scans of all patients. Using Pyradiomics, 120 radiomic features were extracted from each image. The key radiomic features screened by different classifiers varied and lead to significant differences in classification accuracy. The LASSO achieved the best performance (sensitivity: 72.2%, specificity: 75.1%, and AUC: 0.81) on the external validation dataset and attained excellent agreement (Kappa score: 0.89) with radiologists (average sensitivity: 75.6%, specificity: 78.2%, and AUC: 0.81). All classifiers indicated that "Original_Firstorder_RootMeanSquared" and "Original_Firstorder_Uniformity" were significant features for this task. Conclusions We identified radiomic features that were significantly associated with the classification of COVID-19 pneumonia using multiple classifiers. The quantifiable interpretation of the differences in features between the two groups extends our understanding of CT imaging characteristics of COVID-19 pneumonia.

Selenium (Se) is a potential chemopreventive or chemotherapeutic agent against malignant tumor. Selenium-oligosaccharides are important selenium source of dietary supplementation. Due to the insufficient natural production, it is therefore urgent to develop selenium-oligosaccharides by artificial synthesis. Chitosan, the N-deacetylated derivative of chitin, has been applied widely in biomedical field, owing to its nontoxicity, hydrophilicity, biocompatibility, and biodegradation. While chitosan is water insoluble at neutral pH, limiting its application in physiological conditions. Chitosan oligosaccharide (COS), the hydrolysate of chitosan, is readily soluble in water because of the shorter chain lengths of the oligomers and the free amino groups in the D-glucosamine units. This study was aimed at preparing COS-conjugated selenium (COS-Se) and examining the toxicity and ability on improving immune function and blocking gastric cancer growth. Our results demonstrated that COS-Se displayed directly co-mitogenic and mitogenic actions on mouse splenocytes proliferation in vitro. Besides, COS-Se treatment could effectively elevate phagocytosis and increase the secretion of anti-inflammatory cytokine in mouse peritoneal macrophages. Further in vivo experiments showed that COS-Se exhibited immuno-enhancing effects through promoting the phagocytic index, spleen index and thymus index with no obvious toxicity to Kunming mice. Moreover, COS-Se inhibited proliferation and metastasis of human gastric cancer cells, with non-toxic effects on the normal fibroblast cells in vitro. COS-Se supplementation could significantly repress the growth of gastric adenocarcinoma through reducing levels of CD34, vascular endothelial growth factor and matrix metalloproteinase-9 of nude mice. In conclusion, COS-Se was non-toxic and showed great potential as a functional food ingredient in cancer prevention.

Herein, the effects of carboxymethyl chitosan oligosaccharide (CM-COS) on regulating immunologic function and inhibiting hepatocellular tumor growth were evaluated. Results showed that CM-COS caused dramatic viability loss of hepatocellular carcinoma BEL-7402 with non-toxicity towards normal liver L-02 cells. CM-COS repressed tumor growth of hepatoma-22, and elevated the spleen index and thymus index of tumor-bearing mice. Contents of VEGF and MMP-9 were significantly down-regulated by CM-COS. Histological analyses revealed that CM-COS promoted tumor cell necrosis and produced no significant toxicity to spleen tissues. Moreover, expressions of Caspase-3 in tumor tissues and IL-2 in spleen tissues were significantly activated by CM-COS. Additionally, in vitro cell viability, phagocytic capability and NO production of mouse peritoneal macrophages exposed to CM-COS were significantly higher. CM-COS remarkably increased the in vivo phagocytosing capacity of peritoneal macrophages of Kunming mice. Taken together, our findings suggested that CM-COS might be potentially effective and non-toxic candidate as anti-hepatoma agents.

An extracellular chondroitinase ABC (ChSase ABC) produced by Sphingomonas paucimobilis was purified to homogeneity through ammonium sulfate precipitation, DEAE-Sepharose Fast Flow and Sephadex G-100 chromatography. The molecular weight was 82.3 kDa. It showed specific lyase activity toward chondroitin sulfate A (CS-A), CS-B, CS-C and hyaluronan (HA). Using CS-A as substrate, the specific activity was 98.04 U/mg, the maximal reaction rate (Vmax) and Michaelis-Menten constant (Km) were 0.49 μmol/min/ml and 0.79 mg/ml, respectively. Highest activity was obtained at pH 6.5 and 40 °C, and Hg2+ could strongly inhibit the enzyme activity. Mass spectrometry analysis indicated CS-A was degraded to unsaturated disaccharides by ChSase ABC. In vitro cytotoxic tests showed that CS-A oligosaccharide at the concentration of 50 and 100 μg/ml could promote the proliferation of normal H9c2 myocardial cells, decrease the damage induced by isoproterenol (ISO) and accelerate the recovery of cells injured by ISO. These findings suggested that ChSase ABC from Sphingomonas paucimobilis could be a promising tool for the structural analysis and bioactive oligosaccharide preparation of glucosaminoglycans.

Catechol-functionalized polymers are of particular interest because of their strong water-resistant adhesive properties. Hydroxymethyl chitosan (HECTS) has been used as an implantable biomaterial having good water solubility, biodegradability and biocompatibility. Here, hydrocaffeic acid (HCA) grafted HECTS (HCA-g-HECTS) was prepared through carbodiimide coupling and the tethered catechol underwent periodate ( IO 4 - )-stimulated mono and double cross-linking with genipin. The gelation time of these cross-linked HCA-g-HECTS hydrogels decreased with increasing molar ratio of cross-linker to grafted catechol group, increasing temperature, or the addition of genipin. Under the same molar ratio of cross-linker to catechol, IO 4 - -induced cross-linked HCA-g-HECTS hydrogels exhibited much stronger storage modulus and temperature stability than hydrogels made by Fe3+ -triggered cross-linking. The IO 4 - -stimulated HCA-g-HECTS hydrogels were biocompatible on a cellular level when the molar ratio of IO 4 - to catechol group was less than 0.5:1. The hydrogels prepared with a 0.125:1 molar ratio of IO 4 - to catechol group exhibited high adhesion strength of 73.56 kPa against wet rat skin, and a higher adhesion strength than sutures in a rat wound closure model. This biocompatible IO 4 - -stimulated HCA-g-HECTS hydrogel may represent a promising new tissue adhesive. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 582-593, 2019.

Although various biopolymers and synthetic compounds have been proposed and tested as the vitreous substitutes, no ideal material has been identified yet. In the present study, we developed an in situ-formed hydrogel by crosslinking hydroxypropyl chitosan with alginate dialdehyde. Physical properties of the hydrogel were studied and the cytotoxicity was evaluated using L929 fibroblasts, rabbit corneal endothelial cells and retinal pigment epithelial cells. In a preliminary in vivo study, the hydrogel was employed as vitreous substitute after vitrectomy surgery on rabbits and multiple parameters indicating biosafety and biocompatibility were measured and analyzed postoperatively. Our results showed that the refractive index, transmittance, pH value and density of the hydrogel were similar to those of human vitreous. Cytotoxicity tests demonstrated the hydrogel to be nontoxic to all of the three cell lines selected. Using the rabbit model, we showed that the hydrogel could form in situ and postoperative analysis of slit-lamp observation, intraocular pressure, corneal endothelium examination, B-scan ultrasound and fundus photography showed no significant adverse reactions in the operated eyes during the 90-day follow-up. However, electroretinogram and histopathological examinations indicated minor vision decline and decrease of the densities of cones and rods in the operated rabbit eyes. Collectively, our study suggested that the in situ-formed hydrogel could potentially be used as a vitreous substitute, with its long-term safety and efficacy to be further assessed. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1997-2006, 2018.

Full thickness burns in which the damage penetrates deep into the skin layers and reaches underneath the muscle, compel the need for more effective cure. Herein, cross-linked carboxymethyl-chitosan (CM-chitosan) films, prepared by Schiff base association with oxidized carboxymethyl cellulose (OCMC), are investigated regarding the wound healing capacity on full thickness burn injuries in vivo. Transparent thin CM-chitosan/OCMC films are obtained with tensile strength reaching 6.11 MPa, elongation at break above 27%, and water absorption more than 800%, which operates in favor of absorbing excess exudate and monitoring the wound status. Furthermore, the nonadherent CM-chitosan/OCMC films, with satisfactory biodegradability, cell, and tissue compatibility, are readily used to the wound sites and easily removed following therapy on scalded tissue so as to alleviate the suffering from burn. The films efficiently promote epithelial and dermal regeneration compared to the control, achieving 75.9% and 94.4% wound closure, respectively, after 14 and 27 days. More importantly, CM-chitosan/OCMC films accelerate wound healing with natural mechanisms which include controlling inflammatory response, reducing apoptosis, promoting fibroblast cell proliferation, and collagen formation. In conclusion, the CM-chitosan/OCMC films elevate the repair ratio of burn injuries and have great potential for facilitating the healing process on full-thickness exuding wounds.

In this study, norcantharidin (NCTD), a small-molecule anticancer drug derived from Chinese traditional medicine blister beetle (Mylabris), was conjugated covalently onto carboxymethyl chitosan (CMCS). Then the hepatocellular carcinoma therapeutic properties and liver-protective effects were investigated through orthotopic transplantation tumor model. Results showed that the obtained CMCS-NCTD demonstrated remarkable anti-growth efficacy against hepatocellular 22 in mice. Significant improvement of the liver injury caused by cancer cells was observed in tumor-bearing mice administrated with CMCS-NCTD. Moreover, CMCS-NCTD remarkably increased the serum levels of TNF-α, IFN-γ, TIMP-1 and E-cadherin in mice treated for 12days. Administration of CMCS-NCTD significantly reduced the elevated serum ALT, AST, VEGF and MMP-9 levels of tumor-bearing mice. In addition, activities of SOD and GSH-Px in serum or homogenate of the CMCS-NCTD treated mice were significantly high when compared with model control group. Our data suggested that CMCS-NCTD was a promising candidate as an anti-hepatoma and liver-protection compound.

A novel biodegradable chitin hernia patch was prepared by acetylation of chitosan fabric in our study. Physicochemical properties, cell compatibility and biodegradability of the chitin patch were quantified. Histopathological study of the functional experiment showed that this newly designed hernia patch promoted collagen deposition and neovascularization by significantly promoting the secretion of FGF1 and TGF-β1 in the early postoperative (P

In the present study, galactosylated chitosan (Gal-CS) was conjugated with methoxy poly(ethylene glycol) (mPEG) as a hydrophilic group. The structure of Gal-CS-mPEG polymer was characterized and the nanoparticles (NPs) were prepared using ironic gelation method. The study was designed to investigate the characteristics and functions of Gal-CS-mPEG NPs. The morphology of Gal-CS-mPEG NPs was observed by SEM and it was a compact and spherical shape. The size of the NPs was approximately 200 nm in diameter under the ideal process parameters. The interaction between Gal-CS-mPEG NPs and pDNA, and the protection of pDNA against DNase I and serum degradation by Gal-CS-mPEG NPs were evaluated. Agarose gel electrophoresis results showed that Gal-CS-mPEG NPs had strong interaction with pDNA at the weight ratio of 12:1, 4:1 and 2:1 and could protect pDNA from DNase I and serum degradation. Gal-CS-mPEG NPs exhibited high loading efficiency and sustainable in vitro release. The blood compatibility studies demonstrated that Gal-CS-mPEG NPs had superior compatibility with erythrocytes in terms of aggregation degree and hemolysis level. Gal-CS-mPEG NPs showed no cytotoxicity on L929 cells, which is a normal mouse connective tissue fibroblast, but showed inhibitory effects on the proliferation of Bel-7402 cells, which is a liver cancer cell line. In conclusion, Gal-CS-mPEG NP is a bio-safe and efficient gene carrier with potential application in gene delivery.

Hydroxyethyl chitosan (HECTS) is one of the most important water soluble derivatives of chitosan. In this study, photo-sensitive azidehydroxyethyl chitosan (AZ-HECTS) was synthesized with grafting degree 3.4%, and its water solution resulted in an insoluble hydrogel by 254nm UV irradiation for 90s. AZ-HECTS hydrogels, with water absorption 86.21%, had little impact on growth of mouse fibroblast (L929) and presented good cell biocompatibility. Obvious sudden degradation stage, slow degradation stage and no apparent toxicity was observed after AZ-HECTS hydrogels implanted into rats, and tissue inflammation was slighter, which indicated favorable biological safety. Furthermore, AZ-HECTS hydrogels was loaded with heparin, and released 50% of heparin accumulated 14d. AZ-HECTS-heparin hydrogels showed inhibitory effects on L929, and pro-growth functions within vascular endothelial cells seeded on the hydrogels, meanwhile a positive influence on vascular endothelial growth factor expression. In conclusion, AZ-HECTS hydrogels possessed favorable biocompatibility and biodegradability and had good potential as drug carrier.

Carboxymethyl-chitosan, a water-soluble derivative of chitosan, has emerged as a promising candidate for biomedical applications due to its excellent water solubility, biodegradation, biocompatibility, hydrating, antimicrobial, and nontoxicity. In this paper, the antitumor proliferation and metastasis was studied in vitro and in vivo to evaluate biocompatibility of carboxymethyl-chitosan as biomaterials for antitumor drug delivery. The results showed that carboxymethyl-chitosan could significantly reduce the clone formation and tumor migration of human cancer cells including kidney cancer cell line OS-RC-2, gastric cancer cell line SGC-7901, colon cancer cell line HT-29, and nonsmall cell lung cancer cell line NCI-H1650 in vitro. Through Lewis tumor-bearing C57BL/6 mouse model, carboxymethyl-chitosan was proved to be able to inhibit solid tumor growth and tumor metastasis to the liver and lung, meanwhile increase the level of tissue inhibitor of metalloproteinase 1 and E-cadherin, and decrease the level of mice blood serum matrix metalloproteinase 9. This study suggested that carboxymethyl-chitosan had certain antimetastasis effect and good biocompatibility and may have a potential application as a synergic antitumor reagent.

Cancer is considered to have an adverse influence on health around the world. Chitosan, a linear polysaccharide that contains copolymers of &beta, 1-4 linked d-glucosamine and N-acetyl-d-glucosamine units, has been widely used in the field of biomedicine, owing to its nontoxicity, biocompatibility, biodegradability, and hemocompatibility. This study was aimed at preparing the chitosan oligosaccharides (COS) and examining its ability on suppressing lung cancer in vitro and in vivo. Human non-small-cell lung cancer A549 cells model and C57BL/6 mice bearing lung cancer model were adopted. COS showed inhibition on the viability and proliferation of lung carcinoma cells (A549) in time-dependent manners, but no cytotoxicity to human liver cell (HL-7702). Moreover, COS could significantly increase Bax expression of A549 cells while decreasing Bcl-2 expression. COS supplementation significantly inhibited the growth of Lewis tissues and promoted necrosis of tumor cells in vivo. After treatment with COS, significantly elevated concentrations of Bax and reduced expression of Bcl-2 in tumor tissues, as well as elevated levels of TNF- &alpha, IL-2, Fas and Fas-L in mice serum were observed (p &lt, 0.05). In conclusion, COS had certain anti-tumor effects and potential application as a synergic functional food ingredient to prevent cancer.

The natural biopolymers usually need to be chemically modified by crosslinking reagents to improve their mechanical properties. In the present research, the feasibility of using the dialdehyde carboxymethyl cellulose (DCMC) as a crosslinking reagent was systematically studied. DCMC was prepared by oxidizing carboxymethyl cellulose using sodium periodate. The formation of dialdehyde groups was confirmed by FTIR and the degree of oxidation was determined. The biocompatibility of DCMC was investigated by evaluating its cytotoxicity to L929 fibroblasts and histocompatibility in rat model via intramuscular and subcutaneous injection. DCMC-crosslinked carboxymethyl chitosan (DCMC-CMCTS) was prepared and characterized using the glutaraldehyde-crosslinked CMCTS (GA-CMCTS) as control. The result demonstrated that DCMC was non-cytotoxic, biodegradable and biocompatible. The DCMC-CMCTS displayed significantly better thermostability, swelling capacity and cyto-compatibility compared with GA-CMCTS. Our data provided experimental basis for the future application of DCMC as a novel crosslinking reagent.

Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.

Aiming to enhance therapeutic efficiency and reduce toxic effect of norcantharidin (NCTD), NCTD-conjugated carboxymethyl chitosan (CMCS) conjugates (CNC) were prepared and evaluated for the treatment of hepatocellular carcinoma. In vitro cellular assays revealed that CNC conjugates possessed potent inhibitory effects on the proliferation and migration of BEL-7402 cells. Besides, CNC could change nuclear morphology of tumor cells. In comparison with free NCTD at equivalent dose, CNC exerted enhanced therapeutic efficiency and diminished systemic toxicity in H22 tumor-bearing mice with a tumor inhibition rate of 56.20%. Further investigation about pharmacokinetics and tissue distribution by high performance liquid chromatography (HPLC) analysis indicated that CNC showed a longer retention time in blood circulation and reduced distribution in heart and kidney tissues, thereby exerting different antitumor efficacy and toxicity compared with free NCTD. Our results suggested that CNC conjugates based on CMCS as polymer carriers might be used as a potential clinical alternative for NCTD in tumor therapy.

Carboxymethyl chitosan (CMCS), a water-soluble derivative of chitosan possessing numerous enhanced physicochemical and biological properties, has emerged as a promising biopolymer carrier for new drug delivery. Norcantharidin (NCTD) is an effective anti-tumor compound with severe nephrotoxicity. In this study, norcantharidin-conjugated carboxymethyl chitosan (CMCS-NCTD) was synthesized to reduce systemic toxicity and improve anti-tumor efficiency of NCTD. Our results demonstrated that CMCS-NCTD could significantly inhibit migration of tumor cells both in vitro and in vivo in a dose-dependent manner (P

Carboxymethyl chitosan oligosaccharide (CMCOS), the hydrolytic product of carboxymethyl chitosan, is nontoxic, easily absorbable and good antioxidant. In this study, CMCOS was prepared and its properties in adriamycin nephropathy therapy were investigated. Our results showed that CMCOS had good curative effects on renal function and parenchymal injury induced by adriamycin. CMCOS administration significantly relieved symptoms of proteinuria, hypoalbuminemia, hyperlipidemia, renal hyperplasia and histological lesions in rats (P 0.01). Further exploration for the underlying mechanisms indicated that CMCOS treatment reduced macrophage accumulation, myofibroblast transdifferentiation and podocyte apoptosis. CMCOS treatment could regulate secretions of cytokines (IL-1β, TNF-ɑ and TGF-β1) and improve activities of antioxidative enzymes (SOD, GSH-Px) (P 0.01). In conclusion, therapeutic effects of CMCOS on renal injury mediated by inflammation, fibrosis and oxidative stress made it a good kidney health product and a promising candidate in clinical treatment of human chronic kidney disease.