Hydrophobically Modified Chitosan Research Articles

Hydrophobic modification of biomass chitosan for treatment of oily wastewater and its demulsification mechanism

Traditional demulsifiers are commonly produced using raw materials like ethylene oxide and propylene oxide, which deplete significant petroleum resources and involve hazardous and complex manufacturing processes. In this investigation, a hydrophobically modified chitosan (HMC) was synthesized by grafting dodecyl diethanolamine onto natural chitosan to facilitate the separation of O/W emulsions. Characterization of HMC was conducted using Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance hydrogen spectroscopy (1H NMR) and scanning electron microscopy (SEM). The demulsification efficacy of HMC was assessed through a bottle test in an O/W emulsion containing 0.2 % crude oil. Results showed that at a HMC dosage of 40 mg/L, the light transmission (WT) and oil removal efficiency (WR) of the resulted water phase were 93.4 ± 0.8 % and 99.8 ± 0.1 %, respectively. Furthermore, the competitive adsorption between natural surfactants and HMC at the interface was investigated using interfacial tension (IFT), three-phase contact angle (CA), droplet coalescence time (CTA), and interfacial film substitution. A potential demulsifying mechanism was also proposed, emphasizing HMC’s hydrophilic core and dispersed hydrophobic alkyl chains that enable rapid diffusion to the oil–water interface, replacing interfacial active components to induce demulsification by destabilizing the composite film. The advantages of HMC demulsifier over commercial demulsifiers lie in its superior environmental benefits, diverse range of sources, higher efficiency, and outstanding demulsification performance.

Complexes of an Anionic Surfactant with Chitosan and Its Hydrophobic Derivatives As Disinfectants against SARS-CoV-2

This work is aimed at the preparation of complexes of chitosan and hydrophobically modified (HM) chitosan with an anionic surfactant sodium dodecylbenzene sulfonate (SDBS), and at the study of the virucidal activity of the complexes and their components against SARS-CoV-2. It is shown that the introduction of a sufficient amount (4 mol%) of hydrophobic n-dodecyl side groups provides the activity of HM chitosan against SARS-CoV-2 at moderate concentrations, at which unmodified chitosan and chitosan containing a lower amount of hydrophobic groups do not show any activity. Complexes of HM chitosan with SDBS are prepared, which is proven by fluorescence spectroscopy and isothermal titration calorimetry. It is discovered that HM chitosan/SDBS complex is more active than the polymer without surfactant, and an increase of the amount of hydrophobic groups enhances the activity

Antibacterial chitosan-based composite sponge with synergistic hemostatic effect for massive haemorrhage

Uncontrollable acute bleeding and wound infection pose significant challenges in emergency treatment and surgical operations. Therefore, the research and development of highly efficient antibacterial hemostatic agents are of great importance in reducing the mortality rate among patients with massive hemorrhage. In this study, we utilized hydrophobically modified chitosan (HM-CS) and gallic acid chitosan (GA-CS) to create a composite sponge (HM/GA-CS) that exhibits complementary advantages. The composite sponge combines the alkyl chain and polyphenol structure, allowing it to adsorb blood cells and plasma proteins simultaneously. This synergistic effect was confirmed through various tests, including blood cell adhesion, plasma protein barrier behavior, and in vitro hemostatic testing. Furthermore, experiments conducted on a rat liver injury model demonstrated that the composite sponge achieved rapid coagulation within 52 s, resulting in significantly lower bleeding volume compared with traditional gauze. In addition, the incorporation of GA-CS into HM-CS enhanced the antibacterial properties of the composite sponge. The antibacterial rate of the composite sponge against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) reached 100 % and 98.2 %, respectively. To evaluate its biocompatibility, the composite sponge underwent blood compatibility and cell activity tests, confirming its suitability. The HM/GA-CS sponge holds promising applications in managing cases of massive hemorrhage.

Hydrophobically modified chitosan biopolymer connects halloysite nanotubes at the oil-water interface as complementary pair for stabilizing oil droplets

The integration of cationic and hydrophobic functionalities into hydrophobically modified chitosan (HMC) biopolymer facilitates complementary emulsion stabilization with negatively charged halloysite clay nanotubes (HNT). Oil-in-water emulsions with smaller droplet sizes and significantly improved interfacial resistance to droplet coalescence are obtained on complementary emulsion stabilization by HNT and HMC compared to the individual emulsifiers alone. Contact angle measurements shows that the adsorption of the cationic HMC onto the negatively charged HNT modifies the surface wettability of the nanotubes, facilitating the attachment of the nanotubes to the oil–water interface. High resolution cryo-SEM imaging reveals that free HMC chains locks the nanotubes together at the oil–water interface, creating a high barrier to droplet coalescence. The emulsion stability is an order of magnitude higher for conditions in which the aqueous HNT dispersion is stabilized by the HMC compared to conditions where the negatively charged HNT is strongly flocculated by the cationic HMC. The hydrophobic interaction between HMC chains, insertion of HMC hydrophobes into the oil phase and electrostatic interactions between HMC and HNT are proposed as key mechanisms driving the increased emulsion stability. For potential application as a dispersant system for crude oil spill treatment, the nanotubular morphology of HNT was further exploited for the encapsulation of the water-insoluble surfactant, sorbitan monooleate (Span 80). The HMC and HNT sterically strengthens the oil–water interfacial layer while release of the Span 80 surfactant from the HNT lumen lowers the oil–water interfacial tension. The concepts advanced here are relevant in the development of environmentally-benign dispersants for oil spill remediation.

Influence of DOM characteristics on the flocculation removal of trace pharmaceuticals in surface water by the successive dosing of alum and moderately hydrophobic chitosan

Hydrophobically-modified chitosan (HC) has emerged as a promising flocculant for trace pharmaceutical removal from surface water. However, the variation in the characteristics of dissolved organic matter (DOM) in different water sources influences the efficacy of HC in removing pharmaceutical compounds. In this work, the flocculation performance of sequentially dosing alum and HC (alum+HC) for the treatment of five water types (three synthetic waters, and samples of two real waters collected from the Yangtze River and the Thames River), having different DOM and five representative pharmaceuticals (initial concentration: 100 ng/L), was assessed by bench-scale jar tests. The DOM characteristics were correlated quantitatively with the removal efficiencies (REs) of the pharmaceuticals. Density functional theory computations were performed to illuminate the interfacial interactions in the flocculation. Alum+HC exhibited a remarkably higher RE of all five pharmaceuticals (maximum RE: 73%-95%) from all waters compared to a conventional coagulant or flocculant (alum or polyacrylamide, respectively). In contrast to using HC alone, alum+HC also achieved a higher RE of pharmaceuticals with nearly half the HC dosage, thereby enhancing the cost-effectiveness of the alum+HC dosing system. Among the different key DOM characteristics, the surface charge and molecular weight of DOM had no evident correlation with RE(pharmaceutical), but the hydrophobic/hydrophilic nature and functional group composition of organic carbon of DOM were strongly correlated: Strongly hydrophobic fractions, with C-C & C=C functional groups (binding pharmaceuticals via hydrophobic association), were beneficial, while hydrophilic fractions with C-OH groups were less effective, for pharmaceutical removal. This work showed the enhanced performance of the alum+HC dosing combination in the removal of different pharmaceutical compounds from different waters, and filled the knowledge gap regarding the performance of hydrophobically-modified flocculants in the treatment of different surface water sources.

Antibacterial Activity of N,O-Acylated Chitosan Derivative.

The antibacterial activity of N,O-acylated chitosan derivative with linoleic acid (CH_LA) was tested by disc and well diffusion, agar impregnation and microdilution methods against Staphylococcus aureus, Escherichia coli and Helicobacter pylori strains. Hydrophobically modified chitosan (HMC) was expected to exhibit enhanced antibacterial activity and specific mucin interactions. Although diffusion tests have not indicated the antibacterial potential of chitosan (CH) or CH_LA, the results of the microdilution method demonstrated that tested polymers significantly reduced the amount of living bacteria cells in different concentrations depending on the microorganism. Additionally, CH_LA was characterized by enhanced antibacterial activity compared to CH, which may suggest a different mechanism of interaction with S. aureus and H. pylori. Furthermore, the UV-VIS analysis revealed that the amphiphilic character of derivative led to strong CH_LA–mucin interactions. The study proved the high potential of CH_LA in antibacterial applications, especially for the gastrointestinal tract.

FACTORS ASSOCIATED WITH LATE BLEEDING AFTER A NOVEL RAPID RADIAL HEMOSTASIS STRATEGY USING HYDROPHOBICALLY-MODIFIED CHITOSAN IN CONJUNCTION WITH PNEUMATIC COMPRESSION

Duration of compression post transradial angiography (TRA), varies widely with no current standard. We recently reported first in human pilot data of hydrophobically-modified chitosan (hm-c), an investigational compound that creates a local mucoadhesive hemostatic barrier, plus short pneumatic

Expanding Hydrophobically Modified Chitosan Foam for Internal Surgical Hemostasis: Safety Evaluation in a Murine Model

BackgroundA novel injectable expanding foam based on hydrophobically modified chitosan (HM-CS) was developed to improve hemostasis during surgeries. HM-CS is an amphiphilic derivative of the natural biopolymer chitosan (CS); HM-CS has been shown to improve the natural hemostatic characteristics of CS, but its internal safety has not been systematically evaluated. The goal of this study was to compare the long-term in vivo safety of HM-CS relative to a commonly used fibrin sealant (FS), TISSEEL (Baxter). MethodsSixty-four Sprague–Dawley rats (275-325 g obtained from Charles River Laboratories) were randomly assigned to control (n = 16) or experimental (n = 48) groups. Samples of the test materials (HM-CS [n = 16], CS [n = 16], and FS [n = 16]) applied to a nonlethal liver excision (0.4 ± 0.3 g of the medial lobe) in rats were left inside the abdomen to degrade. Animals were observed daily for signs of morbidity and mortality. Surviving animals were sacrificed at 1 and 6 wk; the explanted injury sites were microscopically assessed. ResultsAll animals (64/64) survived both the 1- and 6-wk time points without signs of morbidity. Histological examination showed a comparable pattern of degradation for the various test materials. FS remnants and significant adhesions to neighboring tissues were observed at 6 wk. Residual CS and HM-CS were observed at the 6 wk with fatty deposits at the site of injury. Minimal adhesions were observed for CS and HM-CS. ConclusionsThe internal safety observed in the HM-CS test group after abdominal implantation indicates that injectable HM-CS expanding foam may be an appropriate internal use hemostatic candidate.

Antimicrobial sponge prepared by hydrophobically modified chitosan for bacteria removal

Hydrophobically modified chitosan (HMCS) prepared by reacting chitosan with dodecyl aldehyde can generate very stable foam when dissolved in mild acidic condition under vigorous mechanical stirring. A durable and lightweight (density of 32 mg/ml) sponge was obtained by freeze-drying the stably formed HMCS foam. In addition to the cationic nature of chitosan, the grafted C12 alkyl chains were also able to help HMCS sponge for capturing E. coli cells (∼4.0 × 108 cells/mg sponge) by intercalating into the outer membrane of E. coli cells. E. coli cells captured on HMCS sponge were found to be mostly dead and easily released into the bulk solution so that the active surface could be continuously regenerated for capturing and killing the rest of alive cells. In comparison with its counterpart (chitosan sponge), HMCS sponge maintained a higher operational stability for the removal of E. coli cells. After 5 repeated cells removal operation, the removal capacity of HMCS sponge could be regenerated back to >90% by thorough washing with ethanol.

Hydrophobically-modified Chitosan Microspheres for Release of Diosgenin

Chitosan microspheres (CS) prepared by water-in-oil emulsion/glutaraldehyde cross-linking-evaporation and simple coacervation/cross-linking with sodium tripolyphosphate were covalently linked to diosgenin hemiesters. The diosgenin content found using elemental analysis was ca. 6 to 42 wt-% and it showed dependence on the type of diosgenin hemiesters and on the method of preparation of the CS microspheres. Fourier transform infrared spectroscopy confirmed the hydrophobic functionalization of CS with the diosgenin hemiesters by amide bond formation. The effect of CS modification with diosgenin on the thermal properties was also studied using differential scanning calorimetry. Microsphere sizes determined using optical microscopy ranged from 60 to 700 um, while scanning electron microscopy depicted morphology dependent on the selected method to obtain CS microspheres. In vitro release studies performed in aqueous medium indicated a drug release dependence on the diosgenin hemiester linkers, the steroid content and the acidity of the solution. Sustained diosgenin release in acidic aqueous solution (pH 6.0) reached from 34 to 81% after 48 h.

Increased Loading, Efficacy and Sustained Release of Silibinin, a Poorly Soluble Drug Using Hydrophobically-Modified Chitosan Nanoparticles for Enhanced Delivery of Anticancer Drug Delivery Systems.

Conventional delivery of anticancer drugs is less effective due to pharmacological drawbacks such as lack of aqueous solubility and poor cellular accumulation. This study reports the increased drug loading, therapeutic delivery, and cellular accumulation of silibinin (SLB), a poorly water-soluble phenolic compound using a hydrophobically-modified chitosan nanoparticle (pCNP) system. In this study, chitosan nanoparticles were hydrophobically-modified to confer a palmitoyl group as confirmed by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) assay. Physicochemical features of the nanoparticles were studied using the TNBS assay, and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analyses. The FTIR profile and electron microscopy correlated the successful formation of pCNP and pCNP-SLB as nano-sized particles, while Dynamic Light Scattering (DLS) and Field Emission-Scanning Electron Microscopy (FESEM) results exhibited an expansion in size between pCNP and pCNP-SLB to accommodate the drug within its particle core. To evaluate the cytotoxicity of the nanoparticles, a Methylthiazolyldiphenyl-tetrazolium bromide (MTT) cytotoxicity assay was subsequently performed using the A549 lung cancer cell line. Cytotoxicity assays exhibited an enhanced efficacy of SLB when delivered by CNP and pCNP. Interestingly, controlled release delivery of SLB was achieved using the pCNP-SLB system, conferring higher cytotoxic effects and lower IC50 values in 72-h treatments compared to CNP-SLB, which was attributed to the hydrophobic modification of the CNP system.

Hydrophobically modified chitosan sponge preparation and its application for anionic dye removal

Via Schiff base reaction, the alkyl chains were grafted to amino groups of chitosan backbone to obtain the hydrophobically modified chitosan (HMCS). The presence of hydrophobic alkyl tails lowers the crystallinity of HMCS but enhances the interaction with hydrophobic adsorbates. HMCS powder exhibited 2-fold higher adsorption capacity (110mgg−1) than chitosan powder toward methyl orange (MO). HMCS can be easily dissolved in mild acid solution and very stable foam was prepared by applying vigorous mechanical stirring to the solution. A robust and non-water wettable sponge was obtained by directly freeze-drying the stable HMCS foam. With enhanced specific surface area, the as-prepared HMCS sponge demonstrated a significantly increased MO adsorption capacity (168mgg−1). The equilibrium adsorption of MO by HMCS sponge follows Langmuir isotherm model and its adsorption kinetic can also be well described by a pseudo-second-order kinetic model.

Synthesis of N-alkylated chitosan and its interactions with blood

When hydrophobically modified chitosan (HM-CHI) comes into contact with red blood cells (RBCs), it can cause agglomeration. This property leads HM-CHI to be a potential agent to form a rapid haemostatic plug to stop bleeding at wound sites. In this study, we investigated the properties of the HM-CHI biopolymer to act as an agent that rapidly clots blood. We have examined the synthesis and structural characteristics of HM-CHI – blood substances using X-ray diffraction, infrared spectroscopy and elemental analysis. To understand the rheological behaviour of RBCs within HM-CHI, we have studied the effects of HM-CHI on RBC aggregation and morphology using a rheometer and scanning electron microscopy (SEM), respectively. When mixed with sodium citrate, HM-CHI rapidly transformed human blood into an elastic gel. In contrast, un-modified chitosan (i.e. without hydrophobes) was unable to clot blood. The hydrophobias within HM-CHI entered into the RBC membranes and connected to the cells by a sample-spanning network, which subsequently led to the formation of an elastic gel. The gelling ability of HM-CHI is similar to that of fibrin-based sealants, but at a much lower cost and greater availability.

Nanoparticle-induced assembly of hydrophobically modified chitosan

Hydrophobically modified chitosan (HMC) self-assembles in solution to form gels, making it suitable for applications in oil dispersion, hydrogel design and wound dressing. The self-assembly of HMC is driven by the association of hydrophobic moieties that are attached to chitosan monomers along the polymer chain. We present the results of discontinuous molecular dynamics simulations aimed at understanding how the length and density of the hydrophobic modification chains attached to HMC affect self-assembly and the structure of the resulting network. Long modification chains are required to promote the formation of a stable network in solution at a modification density of 5%; the networks form more readily at a modification density of 10%. The pore size distribution of the resulting HMC network is relatively independent of the modification chain length and density. Insertion of different sized hydrophobic nanoparticles into HMC has a significant impact on network formation, with the particles acting as junction points that promote the association of several HMC chains. The networks form faster in the presence of many small nanoparticles than in the presence of few large nanoparticles. We conclude that HMC could be a viable candidate to form hydrogels in solution.

Evaluation of hydrophobic chitosan-based particulate formulations of porcine reproductive and respiratory syndrome virus vaccine candidate T cell antigens

PRRS control is hampered by the inadequacies of existing vaccines to combat the extreme diversity of circulating viruses. Since immune clearance of PRRSV infection may not be dependent on the development of neutralising antibodies and the identification of broadly-neutralising antibody epitopes have proven elusive, we hypothesised that conserved T cell antigens represent potential candidates for development of a novel PRRS vaccine. Previously we had identified the M and NSP5 proteins as well-conserved targets of polyfunctional CD8 and CD4 T cells. To assess their vaccine potential, peptides representing M and NSP5 were encapsulated in hydrophobically-modified chitosan particles adjuvanted by incorporation of a synthetic multi-TLR2/TLR7 agonist and coated with a model B cell PRRSV antigen. For comparison, empty particles and adjuvanted particles encapsulating inactivated PRRSV-1 were prepared. Vaccination with the particulate formulations induced antigen-specific antibody responses, which were most pronounced following booster immunisation. M and NSP5-specific CD4, but not CD8, T cell IFN-γ reactivity was measurable following the booster immunisation in a proportion of animals vaccinated with peptide-loaded particles. Upon challenge, CD4 and CD8 T cell reactivity was detected in all groups, with the greatest responses being detected in the peptide vaccinated group but with limited evidence of an enhanced control of viraemia. Analysis of the lungs during the resolution of infection showed significant M/NSP5 specific IFN-γ responses from CD8 rather than CD4 T cells. Vaccine primed CD8 T cell responses may therefore be required for protection and future work should focus on enhancing the cross-presentation of M/NSP5 to CD8 T cells.

Cells capture and antimicrobial effect of hydrophobically modified chitosan coating on Escherichia coli

Hydrophobically modified chitosan (HMCS), prepared by reacting alkyl aldehyde with chitosan was demonstrated to be an effective antimicrobial and transparent coating. The grafted alkyl chains exist as protruded hydrophobic tails on the HMCS coating surface. In contact with E. coli cells, HMCS coating captured and immobilized the cells via these hydrophobic tails. The hydrophobic tails could also kill the cells captured on the coating surface as visualized by fluorescence microscope. More than 50% of the initially loaded cells (2.5×104 CFU) could be killed after 2h contact with HMCS coating. The cells capture and killing effects of the coating surface could be completely neutralized by treating with α-cyclodextrin to sequester the protruded hydrophobic tails. The facile coating of antimicrobial HMCS on surface also enabled the easy fabrication of patterned E. coli cells arrays.

Ion-Specific Self-Assembly of Hydrophobically Modified Polycation of Natural Origin

The effect of two monovalent salts differing in the anions (sodium acetate and sodium chloride) on intermolecular aggregation of fully protonated hydrophobically modified (HM) chitosan in dilute aqueous solutions was studied by light scattering. It was demonstrated that both salts promote the aggregation of similarly charged macromolecules. At the same time, strong ion specificity is observed: acetate ions induce the growth of the aggregates, whereas chloride ions increase the fraction of aggregated chains. The behavior observed was attributed to different mechanisms of interactions of these ions with HM chitosan. Acetate ions possessing higher affinity to chitosan involving electrostatic and hydrophobic interactions as well as hydrogen bonding screen more effectively the electrostatic repulsion between polycationic chains, which allows accommodating more macromolecules within one aggregate. On the other hand, more compact chloride ions seem to promote the formation of crystalline zones within the aggrega...

Hydrophobically Modified Chitosan-Grafted Magnetic Nanoparticles for Bacteria Removal

Hydrophobically modified chitosan (HMCS), synthesized by reacting dodecyl aldehyde with chitosan (CS) has good hemostatic properties and can, by means of its hydrophobic tail, coagulate blood cells. In this work, the ability of synthesized HMCS to coagulate Escherichia coli cells was demonstrated. In order to facilitate the removal of coagulated E. coli cells using an applied magnetic field, HMCS was grafted on to the surface of magnetic nanoparticles (MNPs). Such modified MNPs interacted with Gram-negative bacteria such as E. coli by means of strong hydrophobic forces between the hydrophobic tails of HMCS and outer membrane of E. coli. The highest E. coli removal capacity achieved by MNPs@HMCS was 1.38 × 108 cells/mg. The characterization of CS, HMCS, CS/HMCS grafted MNPs (MNPs@CS, MNPs@HMCS) were carried out by Fourier transform infrared spectroscopy (FTIR), elemental analysis (EA), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The degree of deacetylation (DDA) and the degree...

Simulation Study of Hydrophobically Modified Chitosan as an Oil Dispersant Additive

Hydrophobically modified chitosan (HMC) is being considered as a possible oil dispersant additive to reduce the volume of dispersant required in oil spill remediation. We present the results of discontinuous molecular dynamics (DMD) simulations intended to determine how the HMC architecture affects its ability to prevent oil aggregation. The HMCs have a comb copolymer architecture with hydrophobic side chains (modification chains) of various lengths (5-15 spheres) to represent alkane chains that are attached to the chitosan backbone. We calculated the oil's solvent accessible surface area (SASA), aggregate size distribution, and aggregate asymmetry at various values of the HMC modification chain length, modification density, and concentration to determine HMC efficacy. HMCs with long modification chains result in larger oil SASA than HMCs with short modification chains. For long modification chains, there is no increase in oil SASA with increasing modification density above a saturation value. The size distribution of the oil aggregates depends on the modification chain length; systems with long modification chains lead to large aspherical aggregates, while systems with short modification chains lead to small tightly packed aggregates. A parametric analysis reveals that the most important factor in determining the ability of HMCs to prevent oil aggregation is the interaction between the HMC's modification chains and the oil molecules, even when using short modification chains. We conclude that HMCs with long modification chains are likely to be more effective at preventing oil aggregation than HMCs with short modification chains, and that long modification chains impede spherical oil droplet formation.

Comparison of Sorafenib-Loaded Poly (Lactic/Glycolic) Acid and DPPC Liposome Nanoparticles in the in Vitro Treatment of Renal Cell Carcinoma

The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 μM from 24 to 96 h, respectively. At maximum dosage and time (15 μM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 μM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.