Chitosan Membranes Filled with Cyclosporine A as Possible Devices for Local Administration of Drugs in the Treatment of Breast Cancer.

The aim of this work is the design, preparation and characterization of membranes based on cyclosporine A (CsA) and chitosan carboxylate (CC) to be used as an implantable subcutaneous medical device for a prolonged therapeutic effect in the treatment of breast cancer. The choice to use CsA is due to literature data that have demonstrated its possible antitumor activity on different types of neoplastic cells. To this end, CsA was bound to CC through an amidation reaction to obtain a prodrug to be dispersed in a chitosan-based polymeric membrane. The reaction intermediates and the final product were characterized by Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H-NMR). Membranes were analyzed by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The data obtained showed the effective formation of the amide bond between CsA and CC and the complete dispersion of CsA inside the polymeric membrane. Furthermore, preliminary tests, conducted on MDA-MB-231, a type of breast cancer cell line, have shown a high reduction in the proliferation of cancer cells. These results indicate the possibility of using the obtained membranes as an interesting strategy for the release of cyclosporin-A in breast cancer patients.

Highly sensitive colorimetric sensor for detection of iodine ions using carboxylated chitosan-coated palladium nanozyme.

Although a massive research has been devoted on the exploration of noble metal-based nanozyme, less progress has been made in the investigation of palladium (Pd) nanozyme and the interaction between ions and Pd nanozyme. In this study, a new type of Pd nanozyme was prepared by a facile one-pot approach by using carboxylated chitosan as the stabilizer. Owing to the synergistic effect of carboxylated chitosan stabilized Pd nanoparticles (CC-PdNPs) can effectively catalyze the H2O2-mediated oxidation of 3,3',5,5'-tetramethylbenzidine sulfate (TMB) accompanied by a blue color change (oxidized TMB), indicating the peroxidase-like activity of CC-PdNPs. Furthermore, the Michaelis-Menten constants and catalytic stability of CC-PdNPs render them suitable for environmental analysis and bio-detection. Here, we found that while introducing the iodine ions (I-) into the reaction medium, the peroxidase-like activity of CC-PdNPs has been rapidly and effectively inhibited through the formation of Pd-I bond; thus, the active sites of PdNPs can be blocked by I-. Based on this specific inhibition by I-, a facile colorimetric assay has been performed for the detection of I- with an extremely low limit of detection (0.19 nM). Furthermore, the practicality of the proposed sensor also has been demonstrated in tap water, and the satisfactory recoveries were obtained. Our study not only demonstrated a novel Pd-based nanozyme but also provided guidance for I- sensing for environmental analysis, food inspection, and bio-detection. Graphical abstract.

Novel chitosan-based flocculants for chromium and nickle removal in wastewater via integrated chelation and flocculation.

Carboxylated chitosan (CPCTS) is used as substrates in the design and synthesis of CPCTS-based flocculants through UV-initiated polymerization techniques. The synthesized flocculants are applied to remove Cr and Ni ions from chromic acid lotion and electroplating wastewater through two-stage flocculation. This study investigates the effect of flocculant dosage, pH, reaction time, and stirring speed on the removal efficiency of Cr and Ni ions. Results indicated that the total Cr removal ratios by CPCTS-graft-polyacrylamide-co-sodium xanthate (CAC) and CPCTS-graft-poly [acrylamide-2-Acrylamido-2-methylpropane sulfonic acid] (CPCTS-g-P(AM-AMPS)) are 94.7% and 94.6%, respectively. The total Ni removal efficiencies by CAC and CPCTS-g-P(AM-AMPS) are 99.3% and 99.4%, respectively. The two-stage flocculation with CPCTS-based flocculants could reduce the total concentrations of Cr and Ni to 1.0 mg/L and 0.5 mg/L, respectively. The relationship of removal capacity and structural properties between the flocculants with different functional groups is established through Fourier transform infrared spectroscopy, nuclear magnetic resonance, scanning electron microscopy, and X-ray diffraction. The micro-interfacial behavior between the colloidal particles and the solution during the integrated chelation-flocculation are elucidated. Thus, CPCTS-based flocculants could be a potential material for the removal of high amounts of Cr and Ni ions in industrial wastewater.

Robust, superabsorbent and antibacterial polysaccharide-based hybrid-network hydrogels for wound repair.

Hydrogel dressings with multiple functions are ideal options for wound repair. This study developed hydrogel dressings by interpenetrating the physically crosslinked xanthan gum (XG)/carboxylated chitosan (CCS) network and the chemically crosslinked polyacrylamide (PAAm) network via a one-pot method. The XG-CCS/PAAm hydrogels were found to display tunable mechanical properties, due to the formation of strong network structure. The hydrogels exhibited the strongest tensile strength of 0.6 MPa at an XG/CCS ratio of 40/60, while the largest compressive strength of 4.5 MPa is achieved at an XG/CCS ratio of 60/40. Moreover, the hydrogel with an XG/CCS ratio of 60/40 exhibited desirable adhesion strength on porcine skin, which was 3.7 kPa. It also had a swelling ratio, as high as 1200 %. After loading with cephalexin, the XG-CCS/PAAm hydrogels can deliver the antibacterial drugs following a first-order kinetic. As a result, both E. coli and S. aureus can be completely inactivated by the cefalexin-loaded hydrogels after 12 h. Furthermore, the XG-CCS/PAAm hydrogels were found to exhibit excellent biocompatibility as well as effective wound healing ability, as proven by the in vitro and in vivo tests. In this regard, XG-CCS/PAAm hydrogels can act as promising multifunctional wound dressings.

Carboxylated chitosan improved the stability of phycocyanin under acidified conditions.

Phycocyanin, a natural blue colorant, derived from Spirulina platensis, is now widely used in the food industry. However, its main drawbacks are loss of color and denature of structure in an acidic environment. In this study, carboxylated chitosan (0.1 %-1 % w/v) was chosen as an additive in acid-denatured phycocyanin for preserving phycocyanin's blue color and natural structure. Zeta-potential and particle size revealed that the carboxylated chitosan with high negative charge adsorbed on phycocyanin and provided stronger electrostatic repulsion to overcome the protein aggregation. Ultraviolet-visible absorption spectrum and fluorescence spectroscopy showed that the carboxylated chitosan recovered the microenvironment of tetrapyrrole chromophores and ß-subunits, which led the secondary structure changed and the trimers depolymerized into the monomers changed by the acidic environment. Furthermore, Fourier transform infrared spectroscopy revealed highly negatively charged carboxylated chitosan with the groups (NH2, COOH and OH) could restored the microenvironment of tetrapyrrole chromophores and ß-subunits of phycocyanin, and interact with phycocyanin through hydrogen bonding, NH bonding, ionic bonding and van der Waals, which led to a change in secondary structure and depolymerization of trimers into monomers. Our study demonstrated the carboxylated chitosan played a beneficial role in recovering the structure of acid-denatured phycocyanin and its blue color.

pH-induced complex coacervation of fish gelatin and carboxylated chitosan: Phase behavior and structural properties.

The aim of this study was to investigate the phase behavior and structural properties of fish gelatin complex coacervation with carboxylated chitosan as a function of pH by varying the amount of carboxylated chitosan added (0-0.25%, w/v) while keeping the fish gelatin concentration constant at 0.667% (w/v). Zeta potential indicated that electrostatic interaction drove the complex coalescence of fish gelatin and carboxylated chitosan to form soluble or insoluble complexes. The turbidity of the fish gelatin-carboxylated chitosan complex system was greatest at a carboxylated chitosan concentration of 0.2%. UV and fluorescence spectroscopy indicated that the carboxylated chitosan changed the tertiary conformation of fish gelatin. Circular dichroism showed that complexation of fish gelatin with carboxylated chitosan resulted in a shift from the α-helix to the ß-sheet structure of fish gelatin. In particular, at pH 5, the fish gelatin complexed with carboxylated chitosan had a disordered structure. X-ray diffraction and scanning electron microscopy of the composite coacervates both investigated that electrostatic interaction between the two replaced molecular interaction within the carboxylated chitosan to form a new lamellar porous structure. These findings may in future enable the use of fish gelatin-carboxylated chitosan complex systems in the design of new food matrices.

Hybrid lignin particles via ion-crosslinked for selective removal of anionic dyes from water.

Hybrid lignin (HL) particles were synthesized by compounding lignosulfonate and carboxylated chitosan through a simple ionic cross-linking method, and modifying by polyvinylpolyamine. Due to the synergistic effect of recombination and modification, the material exhibits excellent adsorption performance for anionic dyes in water. The structural characteristics and adsorptive behavior were systematically investigated. The pseudo-second-order kinetic model and the Langmuir model were revealed to well describe the sorption procedure of HL for anionic dyes. The results exhibited that the sorption capacities of HL on sodium indigo disulfonate and tartrazine were 1099.01 mg/g and 436.68 mg/g, respectively. Simultaneously, the adsorbent behaved no significant adsorption capacity loss after five adsorption-desorption cycles, indicating its superb stability and recyclability. Additionally, the HL exhibited excellent selective adsorption of anionic dyes form binary dye adsorption systems. The interaction forces between adsorbent and dye molecules, such as hydrogen bonding, π-π stacking, electrostatic attraction and cation bonding bridge, are discussed in detail. The facile preparation process and superior dyes removal performance of HL were considered a potential adsorbent to remove anionic dyes from wastewater.

Carboxylated chitosan-mediated improved efficacy of mesoporous silica nanoparticle-based targeted drug delivery system for breast cancer therapy.

Nanoparticle-based targeting of overexpressed cell-surface receptors is a promising strategy that provides precise delivery of drugs to cancer cells. In the present study, we developed highly reproducible and monodispersed, chitosan-coated (pH-responsive), doxorubicin-loaded, aptamer-mesoporous silica nanoparticle (MSN) bioconjugates for actively targeting breast cancer cells harboring overexpression of EGF receptors (EGFR/HER2). The developed targeted MSNs demonstrated higher uptake and cytotoxicity of triple negative and HER2 positive breast cancer cells when compared to non-targeted MSNs. The chitosan coating imparted pH-responsiveness and endo/lysosomal escape ability to MSNs, which augmented cytosolic delivery of an anticancer drug. Partial carboxylation of chitosan coated on MSNs allowed for a greater release of drug in a shorter duration of time while retaining pH-responsiveness and endo/lysosomal escape ability. Overall, the coating of carboxylated-chitosan over MSNs enabled tunable drug release kinetics, conjugation of aptamers (targeting agents), and endo/lysosomal escape which together significantly enhanced the efficacy of the developed drug delivery system.

In situ generation of silver nanoparticles and nanocomposite films based on electrodeposition of carboxylated chitosan.

Herein, for the first time the electrodeposition of carboxylated chitosan is studied and utilized for the synthesis of silver nanoparticles (AgNPs) and generation of AgNPs/carboxylated chitosan nanocomposite films. Particularly, AgNPs are in situ synthesized on electrodes or substrates during the electrodeposition. Carboxylated chitosan not only acts as the green reducing agent and stabilizing agent for preparing AgNPs, but also serves as the main component in the electrodeposited nanocomposite film. The experimental results indicate that a smooth and homogeneous film is formed on the silver plate after electrodeposition, and the electrodeposited film can be detached from the silver plate as an independent film. The TEM observation and spectroscopic analysis results confirm the existence of AgNPs (the average size of 10 nm) in the nanocomposite film. The nanocomposite films with various shapes can be fabricated by the spatial selectivity of electrodeposition. In addition, the nanocomposite film containing AgNPs shows favorable antibacterial properties.

Chitosan composite hydrogels cross-linked by multifunctional diazo resin as antibacterial dressings for improved wound healing.

Skin lesions and injuries can increase the risk of pathogen infections. Developing efficacious wound dressings could effectively prevent bacterial infection and accelerate wound healing. Herein, we developed chitosan composite hydrogels cross-linked by multifunctional diazo resin (DR) as antibacterial dressings for improved wound healing. The composite hydrogels were in situ formed by electrostatic interactions, chelation interactions, and covalent bonds between carboxylated chitosan and DR under ultraviolet assisted without small photosensitizer. The resultant hydrogels (noted as DR-CCH) showed good stability at different DR concentrations in physiological buffers. The antibacterial assays showed the DR-CCH could inhibit and kill Escherichia coli and Staphylococcus aureus. What is more, our hydrogels could accelerate wound healing in vivo. The present study demonstrates this composite DR-CCH with trace zinc has potential for accelerated wound healing.

Dual High-Conductivity Networks via Importing a Polymeric Gel Electrolyte into the Electrode Bulk.

To obtain high-ionic-conductivity and high-electron-conductivity electrode materials, we design novel dual high-conductivity networks through importing a polymeric gel electrolyte into the electrode bulk by doping gold nanoparticles, which endows the membrane electrode with not only a high electron conductivity of 1.66 s·cm-1 but also a high ionic conductivity of 2.7 × 10-2 s·cm-1, as well as a good surface area capacitance of 1098 mF·cm-2 at 0.5 mA·cm-2. The membrane electrode shows great mechanical strength, high flexibility, and tremendous stability, and the design concept based on dual conductive networks could be also applied to other electrode systems and other energy storage fields.

Optimization of human-like collagen composite polysaccharide hydrogel dressing preparation using response surface for burn repair.

Collagen and polysaccharide materials have great advantages for burn wound healing and skin regeneration. The purpose of this study was to develop a promising burn dressing. Mixing hyaluronic acid (HA), carboxylated chitosan (CCS) and human-like collagen (HLC) to simulate extracellular matrix (ECM), and glutamine transaminase (TG) was used as a crosslinker. The mechanical properties and pore size of the hydrogel were optimized by response surface methodology. The results showed that the tensile elastic modulus of the hydrogel was 480.43 ± 15.82 kPa, the tensile strain was 55.23 ± 2.43 %, and the pore size was 90.43 ± 5.57 µm. This study constructed a skin burn model and demonstrated that the hydrogel dressing could effectively prevent bacteria infection and confirmed that the hydrogel dressing was more beneficial for promoting burn wound healing than a commercial film (DUO DERM). Therefore, the HLC/HA/CCS hydrogel can be considered a promising burn wound dressing.

High Efficiency Fabrication of Chitosan Composite Nanofibers with Uniform Morphology via Centrifugal Spinning.

While electrospinning has been widely employed to spin nanofibers, its low production rate has limited its potential for industrial applications. Comparing with electrospinning, centrifugal spinning technology is a prospective method to fabricate nanofibers with high productivity. In the current study, key parameters of the centrifugal spinning system, including concentration, rotational speed, nozzle diameter and nozzle length, were studied to control fiber diameter. An empirical model was established to determine the final diameters of nanofibers via controlling various parameters of the centrifugal spinning process. The empirical model was validated via fabrication of carboxylated chitosan (CCS) and polyethylene oxide (PEO) composite nanofibers. DSC and TGA illustrated that the thermal properties of CCS/PEO nanofibers were stable, while FTIR-ATR indicated that the chemical structures of CCS and PEO were unchanged during composite fabrication. The empirical model could provide an insight into the fabrication of nanofibers with desired uniform diameters as potential biomedical materials. This study demonstrated that centrifugal spinning could be an alternative method for the fabrication of uniform nanofibers with high yield.

Development of daidzein nanosuspensions: Preparation, characterization, in vitro evaluation, and pharmacokinetic analysis.

The purpose of this investigation was to improve the solubility and oral bioavailability of daidzein via preparing nanosuspensions (NS) with steric stabilizers, electrostatic stabilizers, or a combination of both. Based on particle size and zeta potential, daidzein NS stabilized by HP-ß-CD, soy lecithin, HP-ß-CD + soy lecithin, TPGS, TPGS + SBE-ß-CD, SDS, or HPMC E5 + SDS were generated and characterized by scanning electron microscopy, powder X-ray diffraction, and Fourier transform-infrared spectroscopy. In addition, the stability, cytotoxicity, solubility, dissolution, and pharmacokinetics of NS were evaluated. The resulting daidzein NS were physically stable and biocompatible and presented as regular shapes with homogenous particle sizes of 360-600 nm and decreased crystallinity. Due to the increased solubility and dissolution rate, the oral bioavailability of daidzein NS in rats was 1.63-2.19 times greater than that of crude daidzein. In particular, among the investigated seven daidzein NS formulations, daidzein NS prepared with the costabilizers HPMC E5 + SDS is an optimal formulation for increased daidzein bioavailability. The present study proposes that the combined usage of steric and electrostatic stabilizers is a promising strategy for improving the bioavailability of water-insoluble flavonoid compounds by an NS approach.