Green and Facile Preparation of Covalent Organic Frameworks Based on Reaction Medium for Advanced Applications.

Covalent organic frameworks (COFs), as a new class of crystalline, well-ordered, and porous materials with intermittent constructions, are formed via organic structural parts connected through covalent bonds. These materials have been employed in several fields comprising pollutant adsorption and separation, catalysis, electrical conductivity, gas storage, etc. The preparation of COFs is mainly applied in tubes with high temperatures and degassing treatment. Furthermore, the reaction medium is involved in toxic organic solvents like toluene, dioxane, mesitylene, acetonitrile, and so on. Hence, discovering clean medium and green approaches has attracted wide attention. Recently, facile, less dangerous, and greener methods have been developed for COFs synthesis in diverse applications like performing the reaction at ambient temperature or employing aqueous solvents, ionic liquids, and a mixture of organic solvents/water. This review article summarizes the eco-friendly production approaches of COFs for diverse applications.

κ-Carrageenan/triazin-based covalent organic framework bionanocomposite: Preparation, characterization, and its application in fast removing of BB41 dye from aqueous solution.

A novel and high efficient adsorbent was prepared based on an environmentally friendly substrate, κ-carrageenan, and a triazine-based covalent organic framework as a co-adsorbent component. Combining these two precursors leads to an effective nanocomposite for removing Basic blue 41 dye from aqueous media. After confirm the structural of prepared composite by various analysis, the adsorption properties were investigated. The optimum conditions were obtained in: pH: 7, temperature: 25 °C and contact time: 210 min; and adsorbent dosage of 10 mg. According to the isotherms study, the basic blue 41 dye adsorption was matched to the Longmuir model with single-layer mechanism. The kinetic of adsorption was studied and fitted with pseudo-second order model with R2 = 0.971. From the results the maximum adsorption capacity of 833 mg/g was obtained in 15 min and the reusability tests showed 24% decrease in yield after three cycles.

Extraction of phenolic compounds from walnut green husk (Juglans regia L.) by Salting-Out extraction method.

Some factors in the salting-out extraction (SOE) method play a major role. The aim of this study was to investigate the interaction effects of the phase forming components and consequently select the best conditions to achieve a highly efficient recovery of phenolic compounds from walnut green husks (Juglans regia L.) using mixtures of ethanol and aqueous ammonium sulfate solutions. According to the results that were analyzed by response surface methodology, the optimal extraction conditions were obtained at ethanol: salt: water ratio of 34.8: 15.1: 54.4 (w/w) at a pH of 6-6.5 and 25 °C. At the optimal conditions, the overall phenolic and flavonoid content, and antioxidant activity were significantly higher than obtained by the conventional method. In addition, at a higher scale (i.e., 5 kg), similar results were obtained. Thus, it can be concluded that SOE has the potential to be scaled up for the simultaneous separation and purification of compounds from plant biomass. This paper is addressing extraction techniques, measurement, and characterization of new natural phenolic compounds from an agricultural by-product and valorization of waste.

Mediator-Free Self-Powered Bioassay for Wide-Range Detection of Dissolved Carbon Dioxide.

Electrochemical sensors for the dissolved CO2 (dCO2) measurement have attracted great interest because of their simple setup and the resulting low costs. However, the developed sensors suffer from the requirement of the external electrical power supply throughout the sensing. Here, the fabrication and evaluation of a self-powered biosensor based on biofuel cells (BFCs) for dCO2 measurements are described. In this device, AuNPs-multiwalled carbon nanotubes/GOx-modified carbon paper (CP) served as a bioanode for the oxidation of glucose, while imine-linked covalent triazine framework (I-CTF)-modified CP was employed as the cathode for the reduction of Fe(CN)63-. I-CTF is a porous organic polymer with a high CO2 capture capacity. Voltammetry and electrochemical impedance spectroscopy confirmed that the electron transfer of Fe(CN)63- on the I-CTF-modified electrode decreases after contacting I-CTF with dCO2. In the designed BFC, by capturing CO2 by the I-CTF-modified cathode, a significant decrease in open-circuit voltage (EOCV) of the BFC was observed, which can be used for the sensitive measurement of dCO2. In addition to the self-powering feature, the EOCV of the BFC sensor can be restored when the captured CO2 is desorbed from the I-CTF-modified cathode by increasing the temperature of the cathode. Finally, the BFC is integrated into a circuit containing a matching capacitor; the charges generated by the BFC are accumulated on the capacitor, and then the instantaneous current is quickly detected using a switching regulator and a digital multimeter. Under optimal conditions, the instantaneous current of the BFC sensor was found to sensitively respond to dCO2 in a wide concentration range from 1.3 × 10-5 to 0.252 atm with a low detection limit of 5 × 10-6 atm.

A novel nanocomposite based on covalent organic polymer and nanocellulose for thin-film microextraction of imipramine from biological samples.

A novel covalent organic polymer was prepared using 1,5-diaminonaphthalene as a linker and cyanuric chloride as a node. A thin-film nanocomposite of 1,5-diaminonaphthalene covalent organic polymer and cellulose nanocrystalline was then fabricated via filtering and casting method. The effect of incorporation of various amounts of 1,5-diaminonaphthalene covalent organic polymer and cellulose nanocrystalline was studied to obtain an efficient nanocomposite thin-film with a large number of polar functional groups and high mechanical stability. Field emission scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectrometry, and thermogravimetric analysis techniques were applied for the characterization of physicochemical properties of the prepared materials. Imipramine was determined in the biological samples using thin-film microextraction followed by gas chromatography flame ionization detection. Parameters affecting the extraction efficiency of imipramine were investigated. Under the optimized conditions, the limit of detection was 0.5 ng/mL. Film-to-film reproducibility for three different films fabricated under the same conditions (at three concentration levels) varied between 8.9 and 9.7%. The linear dynamic range covered more than three orders of magnitude (2-5000 ng/mL) with a determination coefficient of 0.9985. The method was successfully applied for preconcentration and determination of imipramine in biological samples with spiking recoveries between 78 and 93%.

Covalent triazine-based framework-grafted functionalized fibrous silica sphere as a solid-phase microextraction coating for simultaneous determination of fenthion and chlorpyrifos by ion mobility spectrometry.

A novel covalent triazine-based framework (CTF)-grafted phenyl-functionalized fibrous silica nanosphere, KCC-1 (named as RS-2) was synthesized via a simple and effective Friedel-Crafts approach. The microporous CTF with fluorene backbone was coupled and grown uniformly on the surface of phenyl-functionalized KCC-1 to prepare a hybrid extended porous framework. The prepared materials were characterized, and FE-SEM and TEM images revealed a flower-like structure for RS-2. The synthesized RS-2 showed excellent thermal stability, so the weight loss was about 30% at 800 °C. RS-2 was applied as a new coating in the solid-phase microextraction procedure to extract chlorpyrifos and fenthion pesticides from water, wastewater, and fruit samples, before determining by corona discharge-ion mobility spectrometry. Some experimental factors affecting the extraction yield of the analytes, including ionic strength, stirring rate, sample pH, extraction temperature, and extraction time, were investigated. Under optimum conditions, the linear dynamic ranges were 0.1-10 µg L-1 and 1.0-70 µg L-1, and the limits of detection were 0.05 and 0.55 µg L-1 for chlorpyrifos and fenthion, respectively. The proposed method showed recovery values in the range 86-117% with a precision of 3.0-7.1% for real samples. Covalent triazine-based framework (CTF)-grafted phenyl-functionalized fibrous silica nanosphere (named as RS-2) was synthesized. RS-2 was applied as a sorbent for solid-phase microextraction (SPME) of chlorpyrifos and fenthion from fruit and water samples followed by corona discharge ionization ion mobility spectrometry (CD-IMS).

Preparation, characterization and solid-state emission of metal complex-cloisite nanohybrids (MC-C, M = Ru (II) and Cu (II)).

The presence of Na(+) in the Cloisite Na(+) mineral allows modification of its interlayer space to achieve a better compatibility with the host matrix and ion-exchange with a cationic metal complex. The aim of this research is to prepare two new metal complex-Cloisite (MC-C) nanohybrids using reaction of Cloisite Na(+) with the cationic Ru (II) and Cu (II) complexes, [Ru (tpy) 2] (2+) and [Cu (Pir) (phen) (H2O) 2](+), in an aqueous solution for the first time. The X-ray diffraction (XRD) analysis of the modified clays has shown an increase in its interlayer distance as compared to the unmodified Cloisite Na(+). The positions of the basal reflections in the XRD patterns of the modified clays were shifted to a higher d value indicating the expansion in their interlayer distances. The field-emission scanning electron microscopy has shown a homogeneous morphology for the modified clays. The thermal behavior of these novel hybrid materials was also investigated by thermogravimetric analysis. The solid state fluorescence spectra of the modified clays have shown that both cationic complexes exhibit a significant fluorescence emission at room temperature when intercalated into Cloisite.

Fabrication of Polysulfone Beads Containing Covalent Organic Polymer as a Versatile Platform for Efficient Iodine Capture.

Radioactive iodine poses a significant risk to human health, particularly with regard to reproductive and metabolic functions. Designing and developing highly efficient adsorbent materials for radioactive substances remain a significant challenge. This study aimed to address this issue by the fabricating polymeric beads containing covalent organic polymer (COP) as an effective method for removing iodine vapor. To achieve this, a COP was first synthesized via the Friedel-Crafts reaction catalyzed by anhydrous aluminum chloride. Then, COP-loaded polysulfone (PSf) (COP@PSf) and PSf beads were prepared using a phase separation method. The beads produced in this research have exhibited remarkable proficiency in adsorbing iodine vapor, showing an adsorption capacity of up to 216 wt % within just 420 min, which is higher than that of most other similar beads reported in the literature.

Recent advances in the fabrication of organic solvent nanofiltration membranes using covalent/metal organic frameworks.

Organic solvent nanofiltration (OSN) has evolved as a vital technological frontier with paramount significance in the separation and purification of organic solvents. Its implication is particularly prominent in industries such as pharmaceuticals, petrochemicals, and environmental remediation. This comprehensive review, meticulously navigates through the current state of research in OSN membranes, unveiling both the critical challenges and promising opportunities that beckon further exploration. The central focus of this review is on the unique utilization of covalent organic frameworks (COFs) and metal-organic frameworks (MOFs) in OSN membrane design, leveraging their distinctive structural attributes-tunable porosity, robust chemical stability, and molecular sieving capabilities. These qualities position them as exceptional candidates for crafting membranes tailored to the intricacies of organic solvent environments. Our investigation extends into the fundamental principles that render COFs and MOFs adept in OSN applications, dissecting their varied fabrication methods while offering insights into the advantages and limitations of each. Moreover, we address environmental and sustainability considerations in the use of COF and MOF-based OSN membranes. Furthermore, we meticulously present the latest advancements and innovations in this burgeoning field, charting a course toward potential future directions and emerging research areas. By underscoring the challenges awaiting exploration, this review not only provides a panoramic view of the current OSN landscape but also lays the groundwork for the evolution of efficient and sustainable OSN technologies, specifically harnessing the unique attributes of COFs and MOFs.

Recent Advances in Porous Bio-Polymer Composites for the Remediation of Organic Pollutants.

The increasing awareness of the importance of a clean and sustainable environment, coupled with the rapid growth of both population and technology, has instilled in people a strong inclination to address the issue of wastewater treatment. This global concern has prompted individuals to prioritize the proper management and purification of wastewater. Organic pollutants are very persistent and due to their destructive effects, it is necessary to remove them from wastewater. In the last decade, porous organic polymers (POPs) have garnered interest among researchers due to their effectiveness in removing various types of pollutants. Porous biopolymers seem to be suitable candidates among POPs. Sustainable consumption and environmental protection, as well as reducing the consumption of toxic chemicals, are the advantages of using biopolymers in the preparation of effective composites to remove pollutants. Composites containing porous biopolymers, like other POPs, can remove various pollutants through absorption, membrane filtration, or oxidative and photocatalytic effects. Although composites based on porous biopolymers shown relatively good performance in removing pollutants, their insufficient strength limits their performance. On the other hand, in comparison with other POPs, including covalent organic frameworks, they have weaker performance. Therefore, porous organic biopolymers are generally used in composites with other compounds. Therefore, it seems necessary to research the performance of these composites and investigate the reasons for using composite components. This review exhaustively investigates the recent progress in the use of composites containing porous biopolymers in the removal of organic pollutants in the form of adsorbents, membranes, catalysts, etc. Information regarding the mechanism, composite functionality, and the reasons for using each component in the construction of composites are discussed. The following provides a vision of future opportunities for the preparation of porous composites from biopolymers.

Chiral bio-nanocomposites based on thermally stable poly(amide-imide) having phenylalanine linkages and reactive organoclay containing tyrosine amino acid.

Montmorillonite clay modified with the bio-active trifunctional L-tyrosine amino acid salt was used as a reactive organoclay (OC) for the preparation of poly(amide-imide) (PAI)/OC hybrid films. One of the functional groups of the L-tyrosine as the swelling agent formed an ionic bond with the negatively charged silicates, whereas the remaining functional groups were available for further reaction with polymer matrix. The soluble PAI with amine end groups including phenylalanine amino acid was synthesised under green condition using molten tetra-butylammonium bromide by direct polymerization reaction of chiral diacid and 2-(3,5-diaminophenyl)benzimidazole. PAI/OC bio-nanocomposites films containing different contents of OC were prepared via solution intercalation method through blending of OC with the PAI solution. X-ray diffraction and transmission electron microscopy revealed that the dispersion of silicate layers in the PAI created an exfoliated structure as a result of using the trifunctional groups of the swelling agent. The structure and thermal behavior of the synthesised materials were characterized by a range of methods, including X-ray diffraction, Fourier transform infrared spectroscopy, (1)H-NMR, electron microscopy, elemental and thermogravimetric analysis techniques. Thermogravimetric analysis results indicated that the addition of OC into the PAI matrix was increased in the thermal decomposition temperatures of the resulted bio-nanocomposites.

Removal of cationic and anionic dyes using Ca-alginate and Zn-Al layered double hydroxide/metal-organic framework.

In this study, a novel effective bio adsorbent was produced and employed to remove congo red and methylene blue dyes from water matrices. First, Zn-Al layered double hydroxide (Zn-Al LDH) was manufactured in a hydrothermal process. Next, through in-situ nucleation and growing of crystalline NH2-modified Ti metal-organic framework (NH2-MIL-125(Ti) on Zn-Al sheets by solvothermal method, Zn-Al LDH@NH2-MIL-125(Ti) hybrid was produced. The prepared hybrid showed good adsorption capacity (qmax values: 294 mg/g and 158 mg/g) for congo red and methylene blue dyes in optimum condition (adsorbent amount = 5-7 mg, dye concentration = 100-150 mg/L, V = 10 mL, pH = no adjustment, and contact time = 2-5 h). Based on the isotherm and kinetic models, the Langmuir isotherm, as well as the pseudo-second-order model, were fit to the equilibrium data. In the next attempt, to improve the reusability of the powder and particle form of Zn-Al LDH@NH2-MIL-125(Ti) hybrid, as well as prevent of formation of secondary contamination in water, Na-alginate, as a cheap and effective substrate, was used. Novel architectures of robust, reusable, and efficient Ca-alginate/Zn-Al LDH@NH2-MIL-125(Ti) microgel beads were prepared and the performances of the microbeads were compared with pure LDH@NH2-MIL-125(Ti) hybrid.

Comparative study for removal of cationic and anionic dyes using alginate-based hydrogels filled with citric acid-sawdust/UiO-66-NH2 hybrid.

Nowadays, a big challenge is developing a sustainable and effective method for removing contaminants like dyes from aqueous solutions. In this regard, Zr-based metal-organic framework (UiO-66-NH2) and sawdust as the ideal adsorbents were used. Due to their low separation in adsorption processes, embedding into alginate and obtaining composite beads are suggested as a suitable strategy. The achieved Ca-alginate/citric acid (CA)-sawdust/UiO-66-NH2 hydrogel beads were used to compare cationic and anionic dyes removal. This sorbent indicated an excellent selectivity for removing methylene blue versus methyl orange in a binary system. pH = 6, adsorbent amount = 80 mg, methylene blue concentration = 10 mg/L, and contact time = 420 min were achieved as optimal parameters on methylene blue adsorption with an adsorption capacity of about 26 mg/g. The removal process of methylene blue followed linear Freundlich isotherm and nonlinear pseudo-2nd-order kinetic models. The regeneration test demonstrated methylene blue removal efficiency higher than about 89 % after 9 cycles. According to the outcomes, methylene blue could be attached to the adsorbent surface through the electrostatic, hydrogen bonding, and π-π interactions of the aromatic rings. These results confirm the potential of Ca-alginate/CA-sawdust/UiO-66-NH2 hydrogel beads as a selective bio-sorbent for cationic dye removal.

Photosensitive Chitosan-Based Injectable Hydrogel Chemically Cross-Linked by Perylene Bisimide Dopamine with Robust Antioxidant and Cytotoxicity Enhancer Properties for In Vitro Photodynamic Therapy of Breast Cancer.

Here, we report the fabrication of an antioxidant photosensitizing hydrogel system based on chitosan (CS-Cy/PBI-DOPA) covalently cross-linked with perylene bisimide dopamine (PBI-DOPA) as a photosensitizer. The severe insolubility and low tumor selectivity limitations of perylene were overcome by conjugation with dopamine and then to the chitosan hydrogel. The mechanical and rheological study of CS-Cy/PBI-DOPA photodynamic antioxidant hydrogels illustrated interconnected microporous morphologies with high elasticity, swelling ability, and suitable shear-thinning behavior. Bio-friendly properties, such as biodegradability and biocompatibility, excellent singlet oxygen production abilities, and antioxidant properties were also delivered. The antioxidant effects of the hydrogels control the physiological levels of reactive oxygen species (ROS) generated by photochemical reactions in photodynamic therapy (PDT), which are responsible for oxidative damage to tumor cells while protecting normal cells and tissues from ROS damage, including blood and endothelial cells. In vitro, PDT tests of hydrogels were conducted on two human breast cancer cell lines, MDA-MB-231 and MCF-7. These hydrogels offered more than 90% cell viability in the dark and good photocytotoxicity performance with 53 and 43% cell death for MCF-7 and MDA-MB-231 cells, which confirmed their promising potential for cancer therapeutic applications.

Imine-Linked Covalent Organic Frameworks: A Biocompatible and pH-Dependent Carrier for In Vitro Sustained Release of Doxorubicin.

Among the novel drug delivery systems (DDSs), covalent organic frameworks (COFs) show promising features in pharmaceutical science. In this paper, an imine-linked COF with hexagonal topology was synthesized using the autoclave condition. Then, the prepared COF (APB-COF) was used as a pH-dependent carrier for in vitro release of doxorubicin (DOX). The intrinsic properties of APB-COF caused reaching an excellent drug encapsulation efficiency. DOX@APB-COF shows an exemplary pH-dependent release in two different pHs. DOX release at pH = 7.4 was 32%, which increased to 54% by changing the pH to the cancer cell pH (pH = 5.4). Moreover, the cytotoxicity of APB-COF and DOX@APB-COF was studied using the standard MTT test against MCF10 (normal breast cell line) and MDAmb231 cells (breast cancer cell line), respectively. It was observed that the APB-COF does not affect cell proliferation, whereas the DOX@APB-COF only limits cancer cell proliferation. Using APB-COF as the drug carrier can pave the way for using COFs in innovative DDSs.

Multifunctional Bioinspired Bredigite-Modified Adhesive for Bone Fracture Healing.

Despite recent advances in bone adhesives applied for full median sternotomy, the regeneration of bone defects has remained challenging since the healing process is hampered by poor adhesiveness, limited bioactivity, and lack of antibacterial functions. Bioinspired adhesives by marine organisms provide a novel concept to circumvent these problems. Herein, a dual cross-link strategy is employed in designing a multifaceted bioinspired adhesive consisting of a catechol amine-functionalized hyperbranched polymer (polydopamine-co-acrylate, PDA), bredigite (BR) nanoparticles, and Fe3+ ions. The hybrid adhesives exhibit strong adhesion to various substrates such as poly(methyl methacrylate), glass, bone, and skin tissues through synergy between irreversible covalent and reversible noncovalent cross-linking, depending on the BR content. Noticeably, the adhesion strength of hybrid adhesives containing 2 wt % BR nanoparticles to bone tissues is 2.3 ± 0.8 MPa, which is about 3 times higher than that of pure PDA adhesives. We also demonstrate that these hybrid adhesives not only are bioactive and accelerate in vitro bone-like apatite formation but also exhibit antibacterial properties against Staphylococcus aureus, depending on the BR concentration. Furthermore, the superior cellular responses in contact with hybrid adhesives, including improved human osteosarcoma MG63 cell spreading and osteogenic differentiation, are achieved owing to the appropriate ion release and flexibility of the cross-linked double-network adhesive. In summary, multifunctional hybrid PDA/BR adhesives with appreciable osteoconductive, mechanical, and antibacterial properties represent the potential applications for median sternotomy surgery as a bone tissue adhesive.

Post-synthetic modifications of covalent organic frameworks (COFs) for diverse applications.

Covalent organic frameworks (COFs) are porous and crystalline organic polymers, which have found usage in various fields. These frameworks are tailorable through the introduction of diverse functionalities into the platform. Indeed, functionality plays a key role in their different applications. However, sometimes functional groups are not compatible with reaction conditions or can compete and interfere with other groups of monomers in the direct synthetic method. Also, pre-synthesis of bulky moieties in COFs can negatively affect crystal formation. To avoid these problems a post-synthetic modification (PSM) approach is a helpful tactic. Also, with the assistance of this strategy porous size can be tunable and stability can be improved without considerable effect on the crystallite. In addition, conductivity, hydrophobicity/ hydrophilicity, and chirality are among the features that can be reformed with this method. In this review, different types of PSM strategies based on recent articles have been divided into four categories: (i) post-functionalization, (ii) post-metalation, (iii) chemical locking, and (iv) host-guest post-modifications. Post-functionalization and chemical locking methods are based on covalent bond formation while in post-metalation and host-guest post-modifications, non-covalent bonds are formed. Also, the potential of these post-modified COFs in energy storage and conversion (lithium-sulfur batteries, hydrogen storage, proton-exchange membrane fuel cells, and water splitting), heterogeneous catalysts, food safety evaluation, gas separation, environmental domains (greenhouse gas capture, radioactive element uptake, and water remediation), and biological applications (drug delivery, biosensors, biomarker capture, chiral column chromatography, and solid-state smart nanochannels) have been discussed.

Valorization of walnut green husk (Juglans regia L.) through sequential electrohydrodynamic extraction of pectin and phenolics: Process optimization and multidimensional analysis.

This study aimed to optimize the extraction of pectin and phenolics from walnut green husk using the electrohydrodynamic method (EHD) and assess its impact on the chemical structure and properties of pectin. A comparative analysis was conducted with acidified water as the conventional extraction method. The results revealed significant improvements under the optimal EHD conditions (36.8 min, 17.5 kV, 90 °C), leading to a remarkable increase of over 64 % in pectin yield and >20 % in total phenolic content in half the extraction time. Chemical analysis showed that pectin samples contain 1.4-1.7 % ash, 3.6-4.6 % protein, over 90 % carbohydrates, and a galacturonic acid content ranging from 67.7 to 68.2 g/g. Both extraction methods yielded pectin with a high methoxyl degree, comparable thermal stability, and amorphous structure. EHD treatment resulted in reduced molecular weight, degree of esterification, water-holding capacity, and emulsion stability of pectin while enhancing its solubility and emulsion capacity. In summary, EHD treatment significantly improved extraction yield and changed the functionality of pectin, particularly in terms of emulsion activity. This alteration should be considered when utilizing pectin for specific applications.

Influence of fatty acid-esterified waxy maize starch type and concentration on stability and properties of oil-in-water emulsions.

In the current study, native and different fatty acid-esterified waxy maize starches (octanoate, myristoate, and stearoate), followed by an OSA-potato starch (as an industrial emulsifier) were used to prepare sunflower oil-in-water (O/W) emulsion. The effect of emulsifier type and concentration were evaluated on properties of emulsions in terms of mean droplet size, droplet size distribution, and creaming index. To prepare the emulsion, the emulsifier to oil ratios of 1.25 and 0.5 for octanoate and industrial emulsifier (control) were considered as the selected formulations based on the lowest creaming index (2.63 and 0 %, respectively). The influence of various pHs and ionic strengths on droplet size, span and zeta potential value was similar for both produced emulsions. Therefore, the fatty acid-esterified starch could be suggested as a promising environmentally friendly alternative to industrial emulsifiers for fabrication of emulsions with similar stability.

Smart redox-sensitive micelles based on chitosan for dasatinib delivery in suppressing inflammatory diseases.

Dasatinib (DAS) exhibits anti-inflammatory effects by retrieving the balance between inflammatory and anti-inflammatory cytokines secreted by macrophages. The aim of this study was the development of redox-responsive micelles with the potential of passive targeting and on-demand drug release for DAS delivery to macrophages. For this purpose, two molecular weights of chitosan (CHIT) were conjugated to DAS at different molar ratios using 3,3'-dithiodipropionic anhydride (DTDPA) as disulfide bond containing linker to synthesize a series of CHIT-S-S-DAS amphiphilic conjugates. Micelles obtained by the sonication method had particle sizes of 129.3-172.2 nm, zeta potentials of +17.5 to +20.9 mV, drug contents of 0.90-7.20 %, CMC values of 35.3-96.6 µg/ml, and exhibited redox-responsive in vitro drug release. Optimized micelles were non-toxic and dramatically more efficient than non-redox responsive micelles in reducing TNF-α and IL-6 and increasing IL-10 secretion from LPS-stimulated RAW264.7 cells. Furthermore, the redox-responsive micelles were able to reduce the mice paw edema, reduce the plasma levels of pro-inflammatory cytokines and increase plasma level of IL-10, considerably more than free DAS and non-redox responsive micelles in carrageenan-induced mice paw edema model of inflammation.