Quaternary Chitosan Research Articles

Development of functionalized cellulose/wool blended fabrics for high performance textiles

Recently, increasing demands for high quality, high value-added, durable, safe and eco-friendly functional cellulose/wool blended fabrics have stimulated intensive research and development efforts. Therefore, the main goal of the present work was to develop new functional finishing formulations using citric acid/sodium hypophosphite (CA/SHP) cross-linking system along with certain bio-active agents based on triclosan, choline chloride, organosilane quaternary compound or chitosan to get anticrease/antibacterial bi-functionalized blends. Also, CA/SHP and bio-active agent based on AgCl/TiO2 finishing formulation was used to impart anti-crease/anti-bacterial/anti-UV multifunctionalities to the treated fabrics. Type and extent of improvement as well as durability to wash of the imparted function were governed by chemical composition and concentration of the active-additive as well as nature and extent of modification of the treated substrates. SEM images and EDX spectra of some samples were reported. In addition, the tentative reaction mechanisms were also discussed.

Chitosan Derivatives as Bio-based Materials for Paper Heritage Conservation

Three water-soluble chitosan derivatives (ChDs)- carboxymethyl- chitosan (CCh), alkyl-chitosan (ACh), and quaternary-chitosan (QCh)- were evaluated as new materials for paper conservation. Several series of samples were prepared by coating different paper types with ChDs or methylcellulose (MC). The ChDs’ effectiveness were analyzed by their effects on the strength (tensile energy absorption (TEA), double folds) and water barriers (Cobb60, contact angle (CA)). The coatings on laboratory paper showed strength improvements for the CCh/QCh coatings that were consistent with an increase in the coating weight (CW). The ACh had little effect on the strength, but developed an effective barrier to water. The coatings on printing paper were performed at a constant CW by applying two layers of the same ChD or MC, and by combining CCh or QCh in the first layer with ACh in the second layer. Homogenous coatings based on the CCh or QCh resulted in high strength improvements, comparable to MC, but only ACh coatings developed an effective barrier to water. Combinations of the CCh or QCh with ACh provided the best relationship between the strength and barrier properties and proved their effectiveness as strengthening/protective materials in the treatment of natural aged paper.

Synthesis of water soluble quaternary chitosan derivative via protection-deprotection strategy and investigation of its antibacterial effect

New water-soluble trimethyl quaternary derivative of chitosan was synthesized by a multi step processes through protection-deprotection strategy. This derivative was characterized using FTIR and 1H NMR spectroscopy. Finally, the antibacterial effect of this derivative against Gram-negative (Escherichia coli and Salmonella typhimurium) and Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) bacteria in acidic and nutral medium was invetigated. The results of this study demonstrated that this chitosan derivative did not have antibacterial activity against Gram-negative bacteria; however, it showed a relatively good antibacterical effect against Gram-positive bacteria in both acidic and neutral mediums.

Preparation of a porous, magnetic, quaternary chitosan salt by preadsorption and desorption for azo dye adsorption from water

ABSTRACTA porous magnetic quaternary chitosan salt (pre‐CS/EPTAC/Fe3O4) was successfully prepared via a kind of novel method of preadsorption and desorption. The physicochemical properties of pre‐CS/EPTAC/Fe3O4 were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and vibrating sample magnetometry. The adsorption of pre‐CS/EPTAC/Fe3O4 for methyl orange (MO) showed much higher dye uptakes compared with Npre‐CS/EPTAC/Fe3O4 without the preadsorption and desorption of MO, and the maximum adsorption capability for MO was 486.1 mg/g. Adsorption isotherms and adsorption kinetics were well fitted by the Freundlich isotherm model and the pseudo‐second order model, respectively. Thermodynamic parameters, such as the standard free energy change, enthalpy change, and entropy change, were also calculated; this indicated that the adsorption was spontaneous and exothermic. The introduction of MO preadsorption and desorption into the process of preparation improved not only the adsorption of MO but also the adsorption of acid red 1 and orange G. Furthermore, pre‐CS/EPTAC/Fe3O4 particles could be easily regenerated and remained almost constant (98.5%) for six cycles of adsorption and desorption. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43448

Delivery of Splice Switching Oligonucleotides by Amphiphilic Chitosan-Based Nanoparticles.

Splice switching oligonucleotides (SSOs) are a class of single-stranded antisense oligonucleotides (ssONs) being used as gene therapeutics and demonstrating great therapeutic potential. The availability of biodegradable and biocompatible delivery vectors that could improve delivery efficiencies, reduce dosage, and, in parallel, reduce toxicity concerns could be advantageous for clinical translation. In this work we explored the use of quaternized amphiphilic chitosan-based vectors in nanocomplex formation and delivery of splice switching oligonucleotides (SSO) into cells, while providing insights regarding cellular uptake of such complexes. Results show that the chitosan amphiphilic character is important when dealing with SSOs, greatly improving colloidal stability under serum conditions, as analyzed by dynamic light scattering, and enhancing cellular association. Nanocomplexes were found to follow an endolysosomal route with a long lysosome residence time. Conjugation of a hydrophobic moiety, stearic acid, to quaternized chitosan was a necessary condition to achieve transfection, as an unmodified quaternary chitosan was completely ineffective. We thus demonstrate that amphiphilic quaternized chitosan is a biomaterial that holds promise and warrants further development as a platform for SSO delivery strategies.

Simultaneous release of hydrophilic and hydrophobic drugs from modified chitosan nanoparticles

A hydrophilic drug (aspirin) and a hydrophobic drug (probucol), both widely used to treat restenosis, were incorporated into a quaternary ammonium salt-modified chitosan (HACC) using tripolyphosphate (TPP) as the crosslinker. Loading of the two drugs in the HACC nanoparticles was verified by Fourier transform infrared (FTIR) spectra. The physicochemical properties of the drug-loading nanoparticles were examined by differential scanning calorimetry (DSC) and zeta potential measurement. The aspirin and probucol in the HACC matrix existed in amorphous and crystalline phases, respectively. The release behaviors of the two drugs from the HACC nanoparticles were investigated. The HACC nanoparticles loaded with both drugs exhibited higher release rates and larger release amounts of the two drugs than the cases where they were loaded by aspirin or probucol alone. This study provides new insights into drug delivery systems.

Chitosan derivatives as important biorefinery intermediates. Quaternary tetraalkylammonium chitosan derivatives utilized in anion exchange chromatography for perchlorate removal.

There has recently been great interest in the valorization of biomass waste in the context of the biorefinery. The biopolymer chitosan, derived from chitin, is present in large quantities of crustacean waste. This biomass can be converted into value-added products with applications in energy, fuel, chemicals and materials manufacturing. The many reported applications of this polymer can be attributed to its unique properties, such as biocompatibility, chemical versatility, biodegradability and low toxicity. Cost effective water filters which decontaminate water by removal of specific impurities and microbes are in great demand. To address this need, the development of ion exchange resins using environmentally friendly, renewable materials such as biopolymers as solid supports was evaluated. The identification and remediation of perchlorate contaminated water using an easy, inexpensive method has come under the spotlight recently. Similarly, the use of a low cost perchlorate selective solid phase extraction (SPE) cartridge that can be rapidly employed in the field is desirable. Chitosan based SPE coupled with colorimetric analytical methods showed promise as a renewable anion exchange support for perchlorate analysis or removal. The polymers displayed perchlorate retention comparable to the commercial standard whereby the quaternized iron loaded polymer TMC-Fe(III) displayed the best activity.

The effect of substituent, degree of acetylation and positioning of the cationic charge on the antibacterial activity of quaternary chitosan derivatives.

A series of water-soluble cationic chitosan derivatives were prepared by chemoselective functionalization at the amino group of five different parent chitosans having varying degrees of acetylation and molecular weight. The quaternary moieties were introduced at different alkyl spacer lengths from the polymer backbone (C-0, C-2 and C-6) with the aid of 3,6-di-O-tert-butyldimethylsilyl protection of the chitosan backbone, thus allowing full (100%) substitution of the free amino groups. All of the derivatives were characterized using 1H-NMR, 1H-1H COSY and FT-IR spectroscopy, while molecular weight was determined by GPC. Antibacterial activity was investigated against Gram positive S. aureus and Gram negative E. coli. The relationship between structure and activity/toxicity was defined, considering the effect of the cationic group’s structure and its distance from the polymer backbone, as well as the degree of acetylation within a molecular weight range of 7–23 kDa for the final compounds. The N,N,N-trimethyl chitosan with 100% quaternization showed the highest antibacterial activity with moderate cytotoxicity, while increasing the spacer length reduced the activity. Trimethylammoniumyl quaternary ammonium moieties contributed more to activity than 1-pyridiniumyl moieties. In general, no trend in the antibacterial activity of the compounds with increasing molecular weight or degree of acetylation up to 34% was observed.

Quaternary chitosan oligomers enhance resistance and biocontrol efficacy of Rhodosporidium paludigenum to green mold in satsuma orange

This study investigated the capacity of chitosan oligomers (COS), applied before harvest singly or in combination with antagonists, in controlling postharvest green mold caused by Penicillium digitatum in satsuma orange. Oranges treated with COS or Rhodosporidium paludigenum were observed having a delay in onset and progression of disease symptoms relative to wounded controls. Preharvest application of COS at different concentrations achieved similar biocontrol efficiency rates in green mold control after 4 days storage. However, the combination of pre-COS (1%, w/v) and R. paludigenum showed a more effective decay control than any other treatments. COS (1%, w/v) alone did not negatively affect R. paludigenum growth in wounds, but severely inhibited P. digitatum spore germination than lower dose treatments in vitro. The expression levels of the defense-related genes chitinase and phenylalanine ammonia lyase increased with decreased disease symptoms. Moreover, this phenomenon was more prominent in the integrated treatments than in the individual ones.

Novel chitosan-based pH-sensitive and disintegrable polyelectrolyte nanogels

A novel approach to design pH-sensitive and disintegrable polyelectrolyte nanogels composed of citraconic-based N-(carboxyacyl) chitosan (polyanion) and quaternary chitosan (polycation) was reported. Firstly, the hydrolysis of citraconic-modified chitosan was monitored using fluorescamine assay and it could selectively dissociate in acidic media (e.g., pH ∼5.0) due to the isomerization during the addition of citraconic anhydride to chitosan. Secondly, the self-assembly behaviors of different polyelectrolyte pairs between citraconic-based chitosan and quaternary chitosan were investigated via colloidal titration assay. It was indicated that the difference in molecular weight (MW) of opposite charged polyelectrolytes played an important role on the formation of polyelectrolyte nanogels. Results showed that polyelectrolyte nanogels (ca. 300nm in size) only formed when polyanion and polycation had a very large difference in MW. The pH-sensitive behavior of polyelectrolyte nanogels was comprehensively investigated by dynamic light scattering (DLS) and transmission electron microscope (TEM). The incorporation of charge-conversional citraconic-based chitosan into polyelectrolyte complexes has provided an effective approach to prepare polyelectrolyte nanogels which were very stable at neutral pH but disintegrated quickly in acidic media.

Preparation of quaternary ammonium salt of chitosan nanoparticles and their textile properties onAntheraea pernyisilk modification

A novel eco-friendly finishing agent of quaternary chitosan nanoparticles was prepared in two steps from a chitosan with low molecular weight. The water-soluble quaternary ammonium salt of chitosan, N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan chloride (HTCC), was first synthesized in heterogeneous system by quaternization, and then HTCC was further prepared to nanoparticles via ionotropic gelation reaction in the presence of 1, 2, 3, 4-butane tetracarboxylic acid and sodium hypophosphite. The size distribution and morphology of the HTCC particles were characterized using a laser particle size analyzer and transmission electron microscope (TEM). When Antheraea pernyi ( A. pernyi) silk fabric was treated with HTCC nanoparticles by using a conventional dip-pad-dry-cure process, the modified A. pernyi silk fabric demonstrated durable wrinkle-resistant property, shrinkage-resistant property and antimicrobial activities against Staphylococcus aureus and Escherichia coli, even after being exposed to 50 consecutive home-laundering conditions. However, the modification of A. pernyi silk fabric caused breaking strength loss, breaking elongation reduction and initial modulus rise to some extent.

Study of competitive adsorption of acid dyes on magnetic quaternary chitosan salt

Magnetic quaternary chitosan salt CS/EPTAC/Fe3O4 was used for the removal of acid red 1 (AR1), xylenol orange (XO) and alizarin red (AR) in single, binary and ternary systems. In the single system, the maximal adsorption capacity was 781.55 for AR1, 537.40 for XO and 992.61 mg g(-1) for AR at pH 3.0 and 25 °C. The adsorption kinetics of the three dyes followed the pseudo-second-order model. In the multicomponent system, preferential adsorption was observed for AR at low adsorbent quantities due to the small size of the molecule. When the adsorbent amount was greater, AR1 was adsorbed first because of the greater number of sulfonic acid roots. In the entire adsorption process, XO always adsorbed most slowly.

Study on Reactive Dye Wastewater Treatment with Quaternary Chitosan

Chitosan quaternary ammonium salt is synthesized by means of heterogeneous reaction, and then applied to treat reactive dye waste water. Effects of flocculation factors on treatment waste water are discussed. The results show that, the quaternary ammonium salt of chitosan concentration and settling time have great effects on the flocculation effect, and the stirring manner has little effect on flocculation.

Flocculation of Quaternary Chitosan on Acid Dyeing Waste Water

In order to increase the positively charge, solubility in water and grafted degree of chitosan, quaternary chitosan was synthesized with chitosan and glycidyl-trimethyl-ammonium chloride by the heterogeneous reaction. FT-IR was used to characterize the structure of the synthesized. The quaternary chitosan was then used to treat simulated acid dyeing wastewater, the effect of quaternary chitosan concentration, agitation mode and pH values on flocculation were discussed. The results indicated that the H+ in nucleophilic center-NH2 was displaced by-CH2CH(OH)CH2N+(CH3)3 and the 2-hydroxypropyltrimethyl ammonium chloride chitosan (quaternary chitosan) was synthesized. When applied to treatment of acid dye waste water, the decolorization rate was 95.5%, and the COD removal was 86.4%.

Abstract 4519: Lomustine nanoparticles are effective brain cancer treatments.

Abstract Abstract The therapy of brain cancers such as Glioblastoma multiforme (GBM) is often hampered by the blood-brain-barrier, which limits the access of drugs to the brain. High blood concentrations of a drug can increase transport into the brain but in the case of cytotoxic drugs often lead to dose-limiting peripheral toxicity, typically myelosuppression. In the current study we explore the potential of Nanomerics’ Molecular Envelope Technology (MET) nanoparticles to enhance transport of the cytotoxic drug lomustine to the brain while avoiding dose-limiting peripheral bone marrow toxicity. We have previously shown that these particles increase the brain activity of drugs such as the intravenous anaesthetic propofol by a factor of ten. MET nanoparticles were prepared from a self-assembling amphiphilic chitosan based polymer - quaternary ammonium palmitoyl glycol chitosan. Lomustine, a poorly water soluble alkylating nitrosourea (CCNU), was encapsulated within these particles at a concentration of 2mg mL−1, 20x higher than what is achievable with conventional ethanolic- polysorbate 80 formulations. In order to determine the therapeutic efficacy of the formulations, orthotopic intracranial human glioblastomas (U87- MG cells) were studied in female CD-1 nude mice. Established tumours were treated at the maximal achievable lomustine concentrations using MET lomustine (13 mg kg−1/day) and the conventional formulation (1.2 mg kg−1/day) for 10 days. The mean survival time for animals that received the MET formulation was significantly (p <0.05) prolonged (33.17 days) compared to the ethanolic lomustine formulation (22.5 days) and that of the control group (21.33 days). The lack of gross symptoms or any difference in body weight between groups suggested the 10x higher MET nanoparticle lomustine dose did not lead to additional toxicity. This was confirmed measuring full blood and femoral bone marrow cell counts on day 1, 7, and 22 after treatment (regime as before). Animal white blood cell and femoral cell counts were not affected by any of the lomustine formulations, however both treated groups of animals showed a transient drop in the platelet count on Day 7 with recovery by day 22. The MET lomustine particulate formulation thus enabled the administration of a more than ten times higher dose of lomustine which dramatically improved therapeutic outcome with little evidence of any additional toxicity or dose limiting toxic effects. The results of this study suggest that MET nanoparticles may provide a safe means to improve therapeutic outcomes in brain cancer using current cytotoxic drugs. Citation Format: Funmilola A. Fisusi, Ahmed Alzharani, Ian Summers, Julian Morger, Omotunde Okubanjo, Kar wai Chooi, Andreas G. Schätzlein, Ijeoma F. Uchegbu. Lomustine nanoparticles are effective brain cancer treatments. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4519. doi:10.1158/1538-7445.AM2013-4519

Mucoadhesive nanoparticles made of thiolated quaternary chitosan crosslinked with hyaluronan

Mucoadhesive polymeric nanoparticles intended for drug transport across the gastrointestinal mucosa were prepared from quaternary ammonium–chitosan conjugates synthesised from reduced-MW chitosan (32kDa). Conjugates contained pendant moieties of 2–4 adjacent diethyl-dimethylene-ammonium groups substituted on repeating units (26–55%). Conjugates were thiolated via amide bonds with thioglycolic acid to yield products with thiol content in the 35–87μmol/g range. Nanoparticles with mean size in the 270–370nm range and positive zeta-potential (+3.7 to +12.5mV) resulted from ionotropic gelation of the thiolated conjugates with de-polymerised hyaluronic acid (470kDa). The nanoparticles were fairly stable in size and thiol content and showed a significant mucoadhesivity, matching and even exceeding that of the constituent polymers. Nanoparticles were internalised by endothelial progenitor cells in direct relation to their surface charge intensity. Nanoparticle uptake significantly improved cell viability and resistance to oxidation. The lyophilised nanoparticles were re-dispersible and could make a manageable formulation for oral use.

Synthesis and Hydroxyl Radicals Scavenging Activity of 2-Pyridine-acetyl-N-trimethyl Chitosan Chloride

A novel chitosan derivative with double quaternary ammonium salt-2-pyridine-acetyl-N-trimethyl chitosan chloride (PATMCS) was synthesized and the antioxidant activity of PATMCS against hydroxyl radicals was assessed. The results indicated that PATMCS had potent hydroxyl scavenging activity. The <TEX>$IC_{50}$</TEX> of PATMCS was 0.13 mg/mL. PATMCS showed 100% scavenging effect at a dose of 0.8 mg/mL which markedly better than that of N-trimethyl chitosan chloride (TMCS). It was confirmed that quaternary chitosan derivatives showed potent antioxidant activity. PATMCS has double quaternary ammonium salt structure in the molecules. Therefore, the antioxidant activity of PATMCS was better than TMCS. The above results are theoretically fundamental for further development and making use of chitosan resources to prepare new antioxidants.

Preparation and Characterization of Quaternary Chitosan/sodium Alginate Self-Assembled Microcapsules

Biocompatible quaternary chitosan/sodium alginate multilayer microcapsules were prepared by layer-by-layer (LBL) self-assembly on the template of monodispersed melamine formaldehyde resin microspheres (MF). The process of self-assembly was monitored by measuring the surface zeta-potential of colloidal particles. The particle size was determined by digital light scattering (DLS) after each deposition, and the average thickness of monolayer film was revealed to be 3.9 nm. Using rhodamine B-labeled quaternary chitosan as the positive polyelectrolyte and sodium alginate as the negative polyelectrolyte, self-assembled multilayer microcapsules with strong red-light emitting were obtained and observed with fluorescence microscope. The fluorescent microcapsules self-assembled from the biocompatible natural polysaccharides may be potentially applied in drug delivery and fluorescence diagnosis.

Delivery of Peptides to the Blood and Brain after Oral Uptake of Quaternary Ammonium Palmitoyl Glycol Chitosan Nanoparticles

The clinical development of therapeutic peptides has been restricted to peptides for non-CNS diseases and parenteral dosage forms due to the poor permeation of peptides across the gastrointestinal mucosa and the blood-brain barrier. Quaternary ammonium palmitoyl glycol chitosan (GCPQ) nanoparticles facilitate the brain delivery of orally administered peptides such as leucine(5)-enkephalin, and here we examine the mechanism of GCPQ facilitated oral peptide absorption and brain delivery. By analyzing the oral biodistribution of radiolabeled GCPQ nanoparticles, the oral biodistribution of the model peptide leucine(5)-enkephalin and coherent anti-Stokes Raman scattering microscopy tissue images after an oral dose of deuterated GCPQ nanoparticles, we have established a number of facts. Although 85-90% of orally administered GCPQ nanoparticles are not absorbed from the gastrointestinal tract, a peak level of 2-3% of the oral GCPQ dose is detected in the blood 30 min after dosing, and these GCPQ particles appear to transport the peptides to the blood. Additionally, although peptide loaded nanoparticles from low (6 kDa) and high (50 kDa) molecular weight GCPQ are taken up by enterocytes, polymer particles with a polymer molecular weight greater than 6 kDa are required to facilitate peptide delivery to the brain after oral administration. By examining our current and previous data, we conclude that GCPQ particles facilitate oral peptide absorption by protecting the peptide from gastrointestinal degradation, adhering to the mucus to increase the drug gut residence time and transporting GCPQ associated peptide across the enterocytes and to the systemic circulation, enabling the GCPQ stabilized peptide to be transported to the brain. Orally administered GCPQ particles are also circulated from the gastrointestinal tract to the liver and onward to the gall bladder, presumably for final transport back to the gastrointestinal tract.

Equilibrium, kinetic and thermodynamic studies on perchlorate adsorption by cross-linked quaternary chitosan

Cross-linked quaternary chitosan salt (QCS) was used for perchlorate removal from aqueous solution. The effect of pH and co-existing anions on the adsorption process, adsorption isotherms, kinetics and thermodynamics was investigated. The thermo stability and the solubility in water were improved after QCS was cross-linked by glutaraldehyde. The cross-linked QCS showed maximum monolayer adsorption capacity of 119.0mg/g, which was 2.5 times higher than protonated cross-linked chitosan. The adsorption process was almost independent of pH in a range from 4.0 to 10.3, which was much wider than using protonated cross-linked chitosan with applicable pH range of 4.0–6.0. The effect from co-existing anions on perchlorate adsorption followed the order: Cl−>NO3->SO42-. The adsorption data fitted Langmuir and Tempkin isotherm models well. Adsorption kinetic analysis showed that chemical adsorption was a rate-limiting stage during the adsorption process. The adsorption reaction was exothermic and spontaneous according to the calculated result of adsorption thermodynamics. The spent adsorbents could be effectively regenerated by NaCl solution with the concentration higher than 0.3%. Fourier transformation infrared spectra and the change of Cl− concentration in solution demonstrated that the ion-exchange interaction might occur between the chloride ions on the quaternary ammonium salt groups of the cross-linked QCS and the perchlorate ions in solution, resulting in the perchlorate adsorption onto the cross-linked QCS.