Quaternized Chitosan Derivatives Research Articles

Inhibited Bacterial Adhesion and Biofilm Formation on Quaternized Chitosan-Loaded Titania Nanotubes with Various Diameters.

Titania nanotube-based local drug delivery is an attractive strategy for combating implant-associated infection. In our previous study, we demonstrated that the gentamicin-loaded nanotubes could dramatically inhibit bacterial adhesion and biofilm formation on implant surfaces. Considering the overuse of antibiotics may lead to the evolution of antibiotic-resistant bacteria, we synthesized a new quaternized chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) with a 27% degree of substitution (DS; referred to as 27% HACC) that had a strong antibacterial activity and simultaneously good biocompatibility with osteogenic cells. Titania nanotubes with various diameters (80, 120, 160, and 200 nm) and 200 nm length were loaded with 2 mg of HACC using a lyophilization method and vacuum drying. Two standard strain, methicillin-resistant Staphylococcus aureus (American Type Culture Collection 43300) and Staphylococcus epidermidis (American Type Culture Collection 35984), and two clinical isolates, S. aureus 376 and S. epidermidis 389, were selected to investigate the bacterial adhesion at 6 h and biofilm formation at 24, 48, and 72 h on the HACC-loaded nanotubes (NT-H) using the spread plate method, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM). Smooth titanium (Smooth Ti) was also investigated and compared. We found that NT-H could significantly inhibit bacterial adhesion and biofilm formation on its surface compared with Smooth Ti, and the NT-H with 160 nm and 200 nm diameters had stronger antibacterial activity because of the extended HACC release time of NT-H with larger diameters. Therefore, NT-H can significantly improve the antibacterial ability of orthopedic implants and provide a promising strategy to prevent implant-associated infections.

Hydrodynamic behavior of quaternized chitosan at acidic and neutral pH

The study is devoted to estimation of the effect of quaternization on the molecular properties of polysaccharide chitosan. Solution properties of quaternized chitosan derivative, N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan, have been studied in comparison with the initial chitosan in 0.33М СН3СООН + 0.2М CH3СООNa. The averaged quaternization degree of the modified samples was (90 ± 5) %. Hydrodynamics methods, translation isothermal diffusion and viscometry, and static/dynamic light scattering were applied for characterization of two homologues series of chitosans. The equilibrium chain rigidity value and Mark–Kuhn–Houwink relationships for intrinsic viscosity and diffusion coefficient have been received for the both polysaccharides at pH 3.54 and high ionic strength value. A change of thermodynamic conditions in the same solvent was detected for the modified chitosan in relation to initial analog. Even though the side substituents length is longer for the modified polysaccharide, the hydrodynamic dimension of its molecules could be smaller than initial polysaccharide of the same polymerization degree due to nonequivalent contributions of thermodynamic/electrostatic interactions to the total chain rigidity. The hydrodynamic behavior of quaternized chitosan in 0.33М СН3СООН + 0.2М CH3СООNa has been compared to its behavior in 0.2 M NaCl. The influence of the secondary amino group protonation on hydrodynamic properties of modified chitosan molecules was detected at neutral pH. Solution properties of quaternized chitosan in 0.2 M NaCl were identified as the concentration dependent.

Quaternized chitosan particles as ion exchange supports for label-free DNA detection using PNA probe and MALDI-TOF mass spectrometry

Quaternized chitosan particles are introduced as anion-exchanged captures to be used with a conformationally constrained pyrrolidinyl peptide nucleic acid (acpcPNA) and MALDI-TOF mass spectrometry for DNA sequence analysis. Methylated chitosan (MC) and methylated N-benzyl chitosan (MBzC) particles were obtained by heterogeneous chemical modification of ionically cross-linked chitosan particles via direct methylation and reductive benzylation/methylation, respectively. N,N,N-trimethylchitosan (TMC) and N-[(2-hydroxyl-3-trimethylammonium)propyl]chitosan chloride (HTACC) particles were prepared by ionic cross-linking of quaternized chitosan derivatives, homogeneously modified from chitosan, namely TMC and HTACC, respectively. The particles formed had a size in a sub-micrometer range and possessed positive charge. Investigation by MALDI-TOF mass spectrometry suggested that some quaternized particles in combination with acpcPNA were capable of detecting a single mismatched base out of 9–14 base DNA sequences. Potential application of this technique for the detection of wild-type and mutant K-ras DNA, a gene that mutation is associated with certain cancers, has also been demonstrated.

Novel antibacterial electrospun materials based on polyelectrolyte complexes of a quaternized chitosan derivative

Novel antibacterial materials based on polyelectrolyte complexes of quaternized chitosan (TMCh) and poly(2-acrylamido-2-methylpropanesulfonic acid) or poly(acrylic acid) (PAA) were prepared by electrospinning. AgNPs were loaded in TMCh/PAA fibers.

Development of anion-conducting ionomer binder solutions for electrodes of solid alkaline fuel cells.

For solid alkaline fuel cell applications, membrane-electrode assemblies (MEAs) should be prepared. Thus, in this study, anion-conducting ionomer binder was prepared for electrodes of MEAs. Specifically, we synthesized water soluble anionic binder solutions based on quaternized chitosan derivatives (QCDs) and cross-linked QCDs and prepared a novel electrode. The electrochemical and physicochemical properties of ionomer binder and electrode were investigated by FT-IR, NMR and ionic conductivity. The ionic conductivity of these cross-linked QCDs was 9.7 x 10(-3) S cm(-1) in deionized water at room temperature. The membrane electrode assemblies (MEAs) were prepared by a spray method and were investigated in terms of cyclic voltammetry, impedance and fuel cell performance. The MEA with the 35 wt% QCD ionomer showed the highest performance and confirmed the successful formation of ionomer binder at the electrode of the MEA by the on-site crosslinking reaction.

Influence of Hydroxyl Groups of Quaternized Chitosan Derivatives on Antioxidant Activity

Four quaternized chitosan derivatives i. e., N-phenmethyl-N, N-dimethyl chitosan, N-(2-hydroxyl-phenmethyl)-N, N-dimethyl chitosan, N-(4-hydroxyl-phenmethyl)-N, N-dimethyl chitosan and N-(3,4-dihydroxyl-phenmethyl)-N, N-dimethyl chitosan were synthesized and their antioxidant activity against hydroxyl radicals was assessed. The result indicated that all the quaternized chitosan derivatives have better hydroxyl radical scavenging activity than chitosan and the antioxidant activity of derivatives increases when more hydroxyl groups are grafted.

Modifications of Chitosan for Use in Nanoparticulate Drug Delivery Systems

Nanoparticles with naturally occurring biodegradable polymers have emerged as potential carriers of various therapeutic agents. Chitosan, a cationic polysaccharide, is one of such biodegradable polymers, which has been extensively exploited for the preparation of nanoparticles with several therapeutic agents. In recent years, the area of focus has shifted from chitosan to chitosan derivatized polymers due to its vastly improved properties such as better drug retention capability, improved permeation, enhanced mucoadhesion, and sustained release of therapeutic agents. Chitosan derivatized polymers are primarily the quaternized chitosan derivatives, chitosan cyclodextrin complexes, thiolated chitosan, pegylated chitosan, chitosan combined with sugar ligands, chitosan with cholanic acid, chitosan-linolenic acid and chitosan-DTPA. This review article covers the various modifications of chitosan, their preparation procedures and various works done with them. 

Preparation of substituted quaternized arylfuran chitosan derivatives and their antimicrobial activity

Heterocyclic modification of chitosan has been achieved through the formation of a Schiff base intermediate by the reaction of chitosan with substituted arylfurfural. The Schiff bases were further reacted with 10% sodium borohydride followed by reaction with methyl iodide to get the quaternized products. The formation of the Schiff bases and quaternized derivatives has been confirmed by elemental analysis, FTIR, 1H NMR and UV–vis spectroscopy. The compounds are also characterized by thermo-gravimetric analysis. The parent compound and quaternized derivatives were compared for their antibacterial and antifungal activity. The results indicated that quaternized derivatives possess better inhibitory property than chitosan. Further this study confirms that heterocyclic aromatic substituent containing ‘Cl’ and ‘NO2’ are effective in enhancing the antimicrobial activity of Chitosan.

N-alkylation of highly quaternized chitosan derivatives affects the paracellular permeation enhancement in bronchial epithelia in vitro

This study describes the structure–activity relationship for carefully characterized N-alkyl-N-quaternary chitosan derivatives as permeation enhancers for drugs that are mainly absorbed through the paracellular pathway, such as macromolecular drugs and hydrophilic drugs, in a well defined bronchial epithelial cell line. The O-methyl free derivatives used in the study were fully trimethylated (100%) N,N,N-trimethyl chitosan (TMC) and N-propyl-(QuatPropyl), N-butyl-(QuatButyl) and N-hexyl (QuatHexyl)-N,N-dimethyl chitosan, with 85–91% degree of quaternization. The fully trimethylated TMC, from 0.25mg/ml, decreased transepithelial electrical resistance (TER) in a reversible manner and enhanced the permeation of the macromolecule FITC–dextran 4kDa (FD4) 2–5 fold. TMC did not cause any alterations in the tight junction (TJ) protein claudin-4 or in F-actin architecture. QuatHexyl was the most effective polymer to produce enhanced permeation and decreased TER from 0.016mg/ml. Nevertheless, this enhanced permeation was accompanied by reduced viability and dissociation of F-actin and claudin-4 proteins. The structure–activity relationship suggests that more lipophilic derivatives show more permeation enhancement, TJ disassembly, and less viability in the order of hexyl≈butyl>propyl>methyl and demonstrates that the permeation effect is not only mediated by permanent positive charge but also by the extent of N-alkylation. These results are relevant to elucidate the structural factors contributing to the permeation enhancement of chitosan derivatives and for potential use in pulmonary applications.

Physical characterization and osteogenic activity of the quaternized chitosan-loaded PMMA bone cement

Gentamicin-loaded polymethylmethacrylate (PMMA), widely used for primary cemented arthroplasty and revision surgery for preventing or treating infections, may lead to the evolution of antibiotic-resistant bacteria and dysfunction of osteogenic cells, which further influence the osteointegration of bone cement. In a previous study, we reported that a new quaternized chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) that was loaded into PMMA significantly inhibited the formation of biofilms caused by methicillin-resistant Staphylococcus strains. In the present study, we further investigated the surface morphology, hydrophilicity, apatite formation ability and osteogenic activity of HACC-loaded PMMA. Chitosan-loaded PMMA, gentamicin-loaded PMMA and PMMA without antibiotic were also investigated and compared. The results showed that, compared to other PMMA-based cements, HACC-loaded PMMA had improved properties such as a lower polymerization temperature, prolonged setting time, porous structures after immersion in phosphate-buffered saline, higher hydrophilicity, more apatite formation on the surface after immersion in simulated body fluid, and better attachment and spreading of the human-marrow-derived mesenchymal stem cells. We also found better stem cell proliferation, osteogenic differentiation, and osteogenesis-associated genes expression on the surface of the HACC-loaded PMMA compared to the gentamicin-loaded PMMA. Therefore, this new anti-infective bone cement had improved physical properties and osteogenic activity, which may lead to better osteointegration of the bone cement in cemented arthroplasty.

Antifungal property of quaternized chitosan and its derivatives

Five water-soluble chitosan derivatives were carried out by quaternizing either iodomethane or N-(3-chloro-2-hydroxypropyl) trimethylammonium chloride (Quat188) as a quaternizing agent under basic condition. The degree of quaternization (DQ) ranged between 28±2% and 90±2%. The antifungal activity was evaluated by using disc diffusion method, minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) methods against Trichophyton rubrum (T. rubrum), Trichophyton mentagrophyte (T. mentagrophyte), and Microsporum gypseum (M. gypseum) at pH 7.2. All quaternized chitosans and its derivatives showed more effective against T. rubrum than M. gypseum and T. mentagrophyte. The MIC and MFC values were found to range between 125–1000μg/mL and 500–4000μg/mL, respectively against all fungi. Our results indicated that the quaternized N-(4-N,N-dimethylaminocinnamyl) chitosan chloride showed highest antifungal activity against T. rubrum and M. gypseum compared to other quaternized chitosan derivatives. The antifungal activity tended to increase with an increase in molecular weight, degree of quaternization and hydrophobic moiety against T. rubrum. However, the antifungal activity was depended on type of fungal as well as chemical structure of the quaternized chitosan derivatives.

Non‐Woven Fibrous Materials with Antibacterial Properties Prepared by Tailored Attachment of Quaternized Chitosan to Electrospun Mats from Maleic Anhydride Copolymer

In order to impart antibacterial properties to microfibrous electrospun materials from styrene/maleic anhydride copolymers, quaternized chitosan derivatives (QCh) containing alkyl substituents of different chain lengths are covalently attached to the mats. A complete inhibition of the growth of bacteria, S. aureus (Gram-positive) and E. coli (Gram-negative), for a contact time of 30–120 min or a decrease of the bacterial titer by 2–3 log units is observed depending on the quaternization degree, the chain length of the alkyl substituent, and the molar mass of QCh. The modified mats are also effective in suppressing the adhesion of pathogenic S. aureus bacteria.

Recent Advancement of Chitosan-Based Nanoparticles for Oral Controlled Delivery of Insulin and Other Therapeutic Agents

Nanoparticles composed of naturally occurring biodegradable polymers have emerged as potential carriers of various therapeutic agents for controlled drug delivery through the oral route. Chitosan, a cationic polysaccharide, is one of such biodegradable polymers, which has been extensively exploited for the preparation of nanoparticles for oral controlled delivery of several therapeutic agents. In recent years, the area of focus has shifted from chitosan to chitosan derivatized polymers for the preparation of oral nanoparticles due to its vastly improved properties, such as better drug retention capability, improved permeation, enhanced mucoadhesion and sustained release of therapeutic agents. Chitosan derivatized polymers are primarily the quaternized chitosan derivatives, chitosan cyclodextrin complexes, thiolated chitosan, pegylated chitosan and chitosan combined with other peptides. The current review focuses on the recent advancements in the field of oral controlled release via chitosan nanoparticles and discusses about its in vitro and in vivo implications.

Contact‐Killing Polyelectrolyte Microcapsules Based on Chitosan Derivatives

AbstractPolyelectrolyte‐multilayer microcapsules are made by layer‐by‐layer (LbL) assembly of oppositely charged polyelectrolytes onto sacrificial colloidal particles, followed by core removal. In this paper, contact‐killing polyelectrolyte microcapsules are prepared based solely on polysaccharides. To this end, water‐soluble quaternized chitosan (QCHI) with varying degrees of substitution (DS) and hyaluronic acid (HA) are assembled into thin films. The quaternary ammonium groups are selectively grafted on the primary amine group of chitosan by exploiting its reaction with glycidyltrimethylammonium chloride (GTMAC) under homogeneous aqueous acidic conditions. The morphology of the capsules is closely dependent on the DS of the quaternized chitosan derivatives, which suggests differences in their complexation with HA. The DS is also a key parameter to control the antibacterial activity of QCHI against Escherichia Coli (E. coli). Thus, capsules containing the QCHI derivative with the highest DS are shown to be the most efficient to kill E. coli while retaining their biocompatibility toward myoblast cells, which suggests their potential as drug carriers able to combat bacterial infections.

Potential prospects of chitosan derivative trimethyl chitosan chloride (TMC) as a polymeric absorption enhancer: synthesis, characterization and applications

In recent years, researchers have been working extensively on various novel properties of polymers to develop increased efficiency of drug delivery and improve bioavailability of various drug molecules, especially macromolecules. Chitosan, a naturally occurring polysaccharide, because of its protonated/polymeric nature, provides effective and safe absorption of peptide and protein drugs. Its transmucosal absorption is, however, limited to acidic media because of its strong intermolecular hydrogen bonds. A new partially quaternized chitosan derivative, N-trimethyl chitosan chloride (TMC), has been synthesized with improved solubility, safety and effectiveness as an absorption enhancer at neutral pH and in aqueous environment. It enhances the absorption, especially of peptide drugs, by reversible opening of tight junctions in between epithelial cells, thereby facilitating the paracellular diffusion of peptide drugs. This derivative thus opens new perspectives as a biomaterial for various pharmaceutical applications/drug delivery systems. This review deals with the potential use of the quaternized chitosan derivative as a permeation enhancer for the mucosal delivery of macromolecular drugs along with its other biomedical applications.

Anion-exchange membranes composed of quaternized-chitosan derivatives for alkaline fuel cells

A series of quaternized-chitosan derivatives (QCDs) with various degrees of quaternization was synthesized using glycidyltrimethylammonium chloride as a main quaternized reagent. These QCDs were then processed into hydroxide—form quaternary ammonium salts with aqueous potassium hydroxide solutions. The resultant hydroxide—form QCD gels were further crosslinked into anion-exchange membranes using ethylene glycol diglycidyl ether. The crosslinking density, crystallinity, swelling index, ion exchange capacity, ionic conductivity and thermal stability of the crosslinked membranes were subsequently investigated. It was found that properties of crosslinked membranes were modulated mainly by the degree of quaternization and crosslinking density of membranes. Some membranes exhibited promising characteristics and had the potential for applications in alkaline polymer electrolyte fuel cells in considering their integrative properties.

Nanoparticles of quaternized chitosan derivatives as a carrier for colon delivery of insulin: Ex vivo and in vivo studies

The aim of the present study was to develop insulin nanoparticulate systems by using chitosan (CS), triethylchitosan (TEC) and dimethyl-ethylchitosan (DMEC, a new quaternized derivative of chitosan) for colon delivery. The nanoparticles were prepared by the polyelectrolyte complexation (PEC) method. Particle size distribution, zeta potential and polydispersity index of the nanoparticles were determined using dynamic light scattering technique. Transmission electron microscopy (TEM) was also used to observe the morphology of the nanoparticles. It was found that the nanoparticles carried positive charges and showed a size distribution in the range of 170–270 nm with spherical morphology and smooth surface structure. The amount of insulin loaded into the nanoparticles was determined by measuring the association efficiency and also the content of insulin in the nanoparticles. Insulin loading was found to be more than 80% for all of the nanoparticles. In vitro release studies showed a small burst effect at the beginning and then a sustained release characteristic for 5 h. Ex vivo investigations revealed better insulin transport across the colon membrane of rats for nanoparticles made with quaternized derivatives than those made of chitosan. In vivo studies in rats have showed enhanced colon absorption of insulin by using these nanoparticles compared to free insulin in diabetic rats. The insulin absorption from the rat's colon was evaluated by its hypoglycemic effect.

The influence of the cationic of quaternized chitosan on antifungal activity

Quaternized chitosan: N-(2-hydroxyl-phenyl)- N, N-dimethyl chitosan (NHPDCS), N-(5-chloro-2-hydroxyl-phenyl)- N, N-dimethyl chitosan (NCHPDCS), N-(2-hydroxyl-5-nitro-phenyl)- N, N-dimethyl chitosan (NHNPDCS) and N-(5-bromic-2-hydroxyl-phenyl)- N, N-dimethyl chitosan (NBHPDCS) were synthesized and their antifungal activities against Botrytis cinerea Pers. ( B. cinerea Pers.) and Colletotrichum lagenarium (Pass) Ell.et halst ( C. lagenarium (Pass) Ell.et halst) were investigated. The results indicated that the quaternized chitosan derivatives had better inhibitory effects than chitosan, and the antifungal activities should be affected by the cation in these compounds.

The influence of molecular weight of quaternized chitosan on antifungal activity

Quaternized chitosan derivatives with different molecular weights were synthesized in the laboratory. Subsequent experiments were conducted to test their antifungal activities against Botrytis cinerea Pers. ( B. cinerea pers.) and Colletotrichum lagenarium (Pass) Ell.et halst ( C. lagenarium (Pass) Ell.et halst). Our results indicate that quaternized chitosan derivatives have stronger antifungal activities than chitosan. Furthermore, quaternized chitosan derivatives with high molecular weight are shown to have even stronger antifungal activities than those with low molecular weight.

Novel antibacterial fibers of quaternized chitosan and poly(vinyl pyrrolidone) prepared by electrospinning

The preparation of continuous defect-free fibers from quaternized chitosan derivative (QCh) has been achieved by electrospinning of mixed aqueous solutions of QCh with poly(vinyl pyrrolidone) (PVP). The average fiber diameter significantly decreases from 2800 to 1500 nm on increasing the polyelectrolyte content. In order to impart to QCh/PVP electrospun fibers stability to water and water vapor, the fibers have been crosslinked by incorporation of photo-crosslinking additives into QCh/PVP spinning solutions and subsequent UV irradiation of the electrospun fibers. Photo-crosslinked QCh-containing electrospun mats show high antibacterial activity against the Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli.