Research progress on chitosan and its derivatives in the fields of corrosion inhibition and antimicrobial activity.

Chitosan stands out as the only known polysaccharide of its kind, second only to cellulose. As the second-largest biopolymer globally, chitosan and its derivatives are extensively used in diverse areas such as metal anti-corrosion prevention, food production, and medical fields. Its benefits include environmental friendliness, non-toxicity, cost-effectiveness, and biodegradability. Notably, the use of chitosan and its derivatives has gained substantial attention and has been extensively researched in the fields of metal anti-corrosion prevention and antibacterial applications. By means of chemical modification or synergistic action, the inherent limitations of chitosan can be substantially improved, thereby enhancing its biological and physicochemical properties to meet a wider range of applications and more demanding application requirements. This article offers a comprehensive review of chitosan and its modified composite materials, focusing on the enhancement of their anticorrosion and antibacterial properties, as well as the mechanisms by which they serve as anticorrosion and antibacterial agents. Additionally, it summarizes the synthesis routes of various modification methods of chitosan and their applications in different fields, aiming to contribute to the interdisciplinary development and potential applications of chitosan in various areas.

The Chemical Modification to Improve Solubility of Chitosan and Its Derivatives Application, Preparation Method, Toxicity as a Nanoparticles.

Chitosan is a functional polymer in the pharmaceutical field, including for nanoparticle drug delivery systems. Chitosan-based nanoparticles are a promising carrier for a wide range of therapeutic agents and can be administered in various routes. Solubility is the main problem for its production and utilization in large-scale industries. Chitosan modifications have been employed to enhance its solubility, including chemical modification. Many reviews have reported the chemical modification but have not focused on the specific characteristics obtained. This review focused on the modification to improve chitosan solubility. Additionally, this review also focused on the application of chitosan derivatives in nanoparticle drug delivery systems since very few similar reviews have been reported. The specific method for chitosan derivative-based nanoparticles was also reported and the latest report of chitosan, chitosan derivative, and chitosan toxicity were also described.

Highly Potent Cationic Chitosan Derivatives Coupled to Antimicrobial Peptide Dendrimers to Combat Pseudomonas aeruginosa.

The burden of bacterial wound infections has considerably increased due to antibiotic resistance to most of the currently available antimicrobial drugs. Herein, for the first time, a chemical coupling of two cationic N-aryl (pyridyl and aminocinnamyl) chitosan derivatives to antimicrobial peptide dendrimers (AMPDs) of different generations (first, second, and third) via thioether-haloacetyl reaction is reported. The new chitosan-AMPD conjugates show high selectivity by killing Pseudomonas aeruginosa and very low toxicity toward mammalian cells, as well as extremely low hemolysis to red blood cells. Electron microscopy reveals that the new chitosan derivatives coupled to AMPD destroy both the inner and outer membranes of Gram-negative P. aeruginosa. Moreover, chitosan-AMPD conjugates show synergetic effects within extremely low concentrations. The new chitosan-AMPD conjugates can be used as potent antimicrobial therapeutic agents, to eradicate pathogens such as those present in acute and chronic infected wounds.

Flame retardant, high mechanical strength, transparent and water-resistant epoxy composites modified with chitosan derivatives.

Adding bio-based flame retardants to improve the flame retardancy of polymer materials without sacrificing other properties is a great challenge. Herein, a novel flame-retardant CS-DOPA was prepared from chitosan and 10-hydroxy-9,10-dihydro-9-oza-10-phosphaphenanthrene-10-oxide by acid-base neutralization reaction and fully characterized. The 4 wt% CS-DOPA modified EP showed good flame retardancy in both gaseous and condensed phase. The peak heat release rate, total smoke production, CO production, and smoke production rate of EP composites containing 4 wt% CS-DOPA were reduced by 55 %, 34 %, 45 %, and 46 %, respectively, to pass the UL-94 V-1 rating with a limiting oxygen index of 34.1 %. The CS-DOPA contributes to the formation of the condensed phase of the thermo-oxidation-resistant high-quality char layer with non-flammable other and phosphorus-containing free radicals released in the gas phase. In addition, EP/4CS-DOPA has good water resistance, mechanical properties, and transparency, with tensile and flexural strength improved by 12.7 % and 13.9 %, respectively, and still has high strength even after water treatment. The present work provides a green and facile strategy to use chitosan as a main raw material to manufacture EP materials with high performance.

Review on chitosan-based antibacterial hydrogels: Preparation, mechanisms, and applications.

Chitosan (CS) is known for its remarkable properties, such as good biocompatibility, biodegradability, and renewability, in addition to its antibacterial and biological activities. However, as CS is insoluble in water, it displays limited antibacterial performance under neutral and physiological conditions. A viable solution to this problem is grafting chemically modified groups onto the CS framework, thereby increasing its solubility and enhancing its antibacterial effect. Herein, the antibacterial action mechanism of CS and its derivatives is reviewed, confirming the prevalent use of composite materials comprising CS and its derivatives as an antibacterial agent. Generally, the antimicrobial ability of CS-based biomaterials can be enhanced by incorporating supplementary polymers and antimicrobial agents. Research on CS-based composite biomaterials is ongoing and numerous types of biomaterials have been reported, including inorganic nanoparticles, antibacterial agents, and CS derivatives. The development of these composite materials has considerably expanded the application of CS-based antibacterial materials. This study reviews the latest progress in research regarding CS-based composite hydrogels for wound repair, tissue engineering, drug release, water purification, and three-dimensional printing applications. Finally, the summary and future outlook of CS-based antibacterial hydrogels are presented in anticipation of a broader range of applications of CS-based antibacterial hydrogels.

Regioselective modification at the 2,3- and 6-positions of chitosan with phenylcarbamates for chromatographic enantioseparation.

Chitosan derivatives with two different phenylcarbamate pendants at the 6-position and 2,3-positions of the glucosamine unit were synthesized by triphenylmethyl as a protective group. The regioselective chitosan derivatives were prepared corresponding to coated-type chiral packed materials (CPMs), which were evaluated with thirteen chiral compounds by high-performance liquid chromatography (HPLC). The regioselective chitosan derivatives (4aⅠ/4aⅡ, 4bⅠ/4bⅡ) bearing electron-withdrawing 3,5­chloro or 4­chloro at the 6-position can recognize 7 or 8 of the 13 enantiomers and achieve baseline separation for enantiomers 5 and 7. They exhibited better chiral recognition abilities than the other derivatives with different substituents at the 6-position and the same 3,5-dimethylphenyl substituent at the 2,3-postion. In comparison to Chit-1 featuring a 3,5-dimethylphenyl substituent at the 2,3- and 6-positions, it was observed that the combination of both an electron-withdrawing and an electron-donating substituent of the regioselective chitosan derivatives (4aⅠ/4aⅡ, 4bⅠ/4bⅡ) showed better or similar enantioseparation abilities for racemic Compounds 7 and 6, respectively. The molecular weight-performance relationship of the regioselective chitosan derivatives was investigated in detail. It was found that with increasing molecular weight, the derivatives 4aⅡ and 4bⅡ all possessed greater enantioseparation power for 4 enantiomers, such as enantiomers 4, 7, 11, and 15, than the corresponding derivatives with low molecular weights. The molecular docking simulation results showed that excellent enantioseparation power significantly depended on the combination and interaction of multiple factors, such as steric hindrance, and polarity of the substituents on the CPMs and enantiomers.

Chitosan as excellent bio-macromolecule with myriad of anti-activities in biomedical applications - A review.

The aim of the study is to explore the myriad of anti-activities of chitosan - deacylated derivative of chitin in biomedical applications. Chitosan consists of reactive residual amino groups, which can be modified chemically to obtain wide range of derivatives. These derivatives exhibit the controlled physicochemical characteristics, which in turn improve its functional properties. Such derivatives find numerous applications in the field of biomedical science, agriculture, tissue engineering, bone regeneration and environmental science. This study presents a comprehensive overview of the multifarious anti-activities of chitosan and its derivatives in the field of biomedical science including anti-microbial, antioxidant, anti-tumor, anti-HIV, anti-fungal, anti- inflammatory, anti-Alzheimer's, anti-hypertensive and anti-diabetic activity. It briefly details these anti-activities with respect to its mode of action, pharmacological effects and potential applications. It also presents the overview of current research exploring novel derivatives of chitosan and its anti- activities in the recent past. Finally, the review projects the prospective potential of chitosan and its derivatives and expects to encourage the readers to develop new drug delivery systems based on such chitosan derivatives and explore its applications in biomedical science for benefit of mankind.

An insight into the effect of interaction with protein on antibacterial activity of chitosan derivatives.

Antimicrobial activity of chitosan in protein-rich media is of a particular interest for various protein-based drug delivery and other systems. For the first time, bacteriostatic activity of chitosan derivatives in the presence of caseinate sodium (CAS) was studied and discussed. Complexation of chitosan derivatives soluble in acidic (CH and RCH) or alkalescent (RCH) media with CAS was confirmed by fluorescent spectroscopy, turbodimetry, light scattering data and measurement of electrical potentials of CAS/chitosan derivative complexes. An addition of CH and RCH caused a static quenching of CAS. Binding constants Kb determined for CH/CAS and RCH/CAS complexes at pH 6.0 were equal to 29.8 × 106 M-1 and 8.9 × 106 M-1, respectively. Kb value of RCH/CAS complex at pH 7.4 was equal to 1.1 × 105'M-1. The poisoned food method was used for counting the number and the direct measurement of the size of bacterial colonies on the surfaces of turbid agar media containing CAS/chitosan derivative complexex. Complete suppression of E. coli cells growth and restriction of S. aureus cells growth were observed on the surface of acidic media. A high concentration of CAS reduced the activity. The activity of RCH in alkalescent media is low or absent. These results can be promising for preparation of microbiologically stable protein-based drug delivery systems.

Preparation and Antioxidant Activity of New Carboxymethyl Chitosan Derivatives Bearing Quinoline Groups.

A total of 16 novel carboxymethyl chitosan derivatives bearing quinoline groups in four classes were prepared by different synthetic methods. Their chemical structures were confirmed by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and elemental analysis. The antioxidant experiment results in vitro (including DPPH radical scavenging ability, superoxide anion radical scavenging ability, hydroxyl radical scavenging ability, and ferric reducing antioxidant power) demonstrated that adding quinoline groups to chitosan (CS) and carboxymethyl chitosan (CMCS) enhanced the radical scavenging ability of CS and CMCS. Among them, both N, O-CMCS derivatives and N-TM-O-CMCS derivatives showed DPPH radical scavenging over 70%. In addition, their scavenging of superoxide anion radicals reached more than 90% at the maximum tested concentration of 1.6 mg/mL. Moreover, the cytotoxicity assay was carried out on L929 cells by the MTT method, and the results indicated that all derivatives showed no cytotoxicity (cell viability > 75%) except O-CMCS derivative 1a, which showed low cytotoxicity at 1000 µg/mL (cell viability 50.77 ± 4.67%). In conclusion, the carboxymethyl chitosan derivatives bearing quinoline groups showed remarkable antioxidant ability and weak cytotoxicity, highlighting their potential use in food and medical applications.

Synthesis and characterization of novel chitosan derivatives (containing dipyridinium quaternary salts) with antimicrobial potential.

Chitosan derivatives are versatile materials, biocompatible and biodegradable, that can be tailor-made to suit specific biomedical applications. In this study, two N-heterocyclic salts (N,N'-diphenacyl-[4,4'-dipyridinium] dibromide (DP) and N,N'-diphenacyl-1,2-bis-(4-pyridinium)ethane dibromide (DPE)) were used for chitosan functionalization to enhance its antimicrobial potential. Physico-chemical characterization of the newly synthesized derivatives (Ch-DP and Ch-DPE) was performed by elemental analysis, spectrometry (UV-Vis, FTIR), electrochemistry (OCP, CV), and electron microscopy (SEM) proving that the highest degree of functionalization was obtained for Ch-DP. The antimicrobial effect of chitosan functionalization was further tested in terms of its interaction with Listeria monocytogenes Scott A, and Staphylococcus aureus ATCC 25923, as Gram-positive bacteria and Escherichia coli ATCC 25922, as Gram-negative bacterium, respectively, showing that the Ch-DP had a good inhibitory activity compared with Ch-DPE.

Anti-Obesity Effects of Chitosan and Its Derivatives.

The number of obese people in the world is rising, leading to an increase in the prevalence of type 2 diabetes and other metabolic disorders. The search for medications including natural compounds for the prevention of obesity is an urgent task. Chitosan polysaccharide obtained through the deacetylation of chitin, and its derivatives, including short-chain oligosaccharides (COS), have hypolipidemic, anti-inflammatory, anti-diabetic, and antioxidant properties. Chemical modifications of chitosan can produce derivatives with increased solubility under neutral conditions, making them potential therapeutic substances for use in the treatment of metabolic disorders. Multiple studies both in animals and clinical trials have demonstrated that chitosan improves the gut microbiota, restores intestinal barrier dysfunction, and regulates thermogenesis and lipid metabolism. However, the effect of chitosan is rather mild, especially if used for a short periods, and is mostly independent of chitosan's physical characteristics. We hypothesized that the major mechanism of chitosan's anti-obesity effect is its flocculant properties, enabling it to collect the chyme in the gastrointestinal tract and facilitating the removal of extra food. This review summarizes the results of the use of COS, chitosan, and its derivatives in obesity control in terms of pathways of action and structural activity.

Advancements in Chitosan-Based Nanoparticles for Pulmonary Drug Delivery.

The evolution of respiratory diseases represents a considerable public health challenge, as they are among the leading causes of death worldwide. In this sense, in addition to the high prevalence of diseases such as asthma, chronic obstructive pulmonary disease, pneumonia, cystic fibrosis, and lung cancer, emerging respiratory diseases, particularly those caused by members of the coronavirus family, have contributed to a significant number of deaths on a global scale over the last two decades. Therefore, several studies have been conducted to optimize the efficacy of treatments against these diseases, focusing on pulmonary drug delivery using nanomedicine. Thus, the development of nanocarriers has emerged as a promising alternative to overcome the limitations of conventional therapy, by increasing drug bioavailability at the target site and reducing unwanted side effects. In this context, nanoparticles composed of chitosan (CS) show advantages over other nanocarriers because chitosan possesses intrinsic biological properties, such as anti-inflammatory, antimicrobial, and mucoadhesive capacity. Moreover, CS nanoparticles have the potential to enhance drug stability, prolong the duration of action, improve drug targeting, control drug release, optimize dissolution of poorly soluble drugs, and increase cell membrane permeability of hydrophobic drugs. These properties could optimize the performance of the drug after its pulmonary administration. Therefore, this review aims to discuss the potential of chitosan nanoparticles for pulmonary drug delivery, highlighting how their biological properties can improve the treatment of pulmonary diseases, including their synergistic action with the encapsulated drug.

New N-Methylimidazole-Functionalized Chitosan Derivatives: Hemocompatibility and Antibacterial Properties.

Novel imidazole derivatives of the low molecular weight chitosan N-(2-hydroxypropyl)-1H-1,2,3-triazol-4-yl)methyl)-1-methyl-1H-imidazol-3-ium chitosan chloride (NMIC) were synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC). The degrees of substitution (DSs) for the new derivatives were 18-76%. All chitosan derivatives (2000 µg/mL) were completely soluble in water. The antimicrobial activity of the new compounds against E. coli and S. epidermidis was studied. The effect of chitosan derivatives on blood and its components was studied. NMIC samples (DS 34-76%) at a concentration <10 µg/mL had no effect on blood and plasma coagulation. Chitosan derivatives (DS 18-76%) at concentrations of ≥83 µg/mL in blood and ≥116.3 µg/mL in plasma resulted in a prolongation of the clotting time of blood and plasma, positively related to the DS. At concentrations up to 9.1 µg/mL, NMIC did not independently provoke platelet aggregation. The degree of erythrocyte hemolysis upon contact with NMIC samples (2.5-2500 µg/mL) was below 4%. The inhibition of blood/plasma coagulation indicates the promising use of the studied samples to modify the surface of medical materials in order to achieve thromboresistance.

Chitosan and Its Structural Modifications for siRNA Delivery.

The use of RNA interference mechanism and small interfering RNA (siRNA) in cancer gene therapy is a very promising approach. However, the success of gene silencing is underpinned by the efficient delivery of intact siRNA into the targeted cell. Nowadays, chitosan is one of the most widely studied non-viral vectors for siRNA delivery, since it is a biodegradable, biocompatible and positively charged polymer able to bind to the negatively charged siRNA forming nanoparticles (NPs) that will act as siRNA delivery system. However, chitosan shows several limitations such as low transfection efficiency and low solubility at physiological pH. Therefore, a variety of chemical and non-chemical structural modifications of chitosan were investigated in the attempt to develop a chitosan derivative showing the features of an ideal siRNA carrier. In this review, the most recently proposed chemical modifications of chitosan are outlined. The type of modification, chemical structure, physicochemical properties, siRNA binding affinity and complexation efficiency of the modified chitosan are discussed. Moreover, the resulting NPs characteristics, cellular uptake, serum stability, cytotoxicity and gene transfection efficiency in vitro and/or in vivo are described and compared to the unmodified chitosan. Finally, a critical analysis of a selection of modifications is included, highlighting the most promising ones for this purpose in the future.

Guanidinylated/PEGylated chitosan in the bioink promotes the formation of multi-layered keratinocytes in a human skin equivalent.

The biological differences of skin between rodent and human beings and the strong appeal to replace the experimental animals have led to the development of alternative models with structures similar to the real human skin. Keratinocytes cultured in vitro on conventional dermal scaffolds tend to form monolayer rather than multi-layer epithelial tissue architectures. How to construct human skin or epidermal equivalents with multi-layered keratinocytes similar to real human epidermis remains one of the greatest challenges. Herein, a human skin equivalent with multi-layered keratinocytes was constructed by 3D bioprinting fibroblasts and subsequent culturing epidermal keratinocytes. Biocompatible guanidinylated/PEGylated chitosan (GPCS) was used as the main component of bioink to 3D bioprint tissue-engineered dermis. The function of GPCS to promote HaCat cell proliferation and connection was confirmed at the genetic, cellular, and histological levels. Compared with the skin tissues with mono-layered keratinocytes engineered with collagen and gelatin, adding GPCS in the bioink generated tissue-engineered human skin equivalents with multi-layered keratinocytes. Such human skin equivalents could be alternative models for biomedical, toxicological, and pharmaceutical research.

Expression Improvement of Recombinant Plasmids of the Interleukin-7 Gene in Chitosan-Derived Nanoparticles and Their Elevation of Mice Immunity.

To investigate a safe and effective approach for enhancing the in vivo expression of recombinant genes and improving the systemic immunity of animals against infectious diseases, we employed the interleukin-7 (IL-7) gene from Tibetan pigs to construct a recombinant eukaryotic plasmid (VRTPIL-7). We first examined VRTPIL-7's bioactivity on porcine lymphocytes in vitro and then encapsulated it with polyethylenimine (PEI), chitosan copolymer (CS), PEG-modified galactosylated chitosan (CS-PEG-GAL) and methoxy poly (ethylene glycol) (PEG) and PEI-modified CS (CS-PEG-PEI) nanoparticles using the ionotropic gelation technique. Next, we intramuscularly or intraperitoneally injected mice with various nanoparticles containing VRTPIL-7 to evaluate their immunoregulatory effects in vivo. We observed a significant increase in neutralizing antibodies and specific IgG levels in response to the rabies vaccine in the treated mice compared to the controls. Treated mice also exhibited increased leukocytes, CD8+ and CD4+ T lymphocytes, and elevated mRNA levels of toll-like receptors (TLR1/4/6/9), IL-1, IL-2, IL-4, IL-6, IL-7, IL-23, and transforming growth factor-beta (TGF-ß). Notably, the recombinant IL-7 gene encapsulated in CS-PEG-PEI induced the highest levels of immunoglobulins, CD4+ and CD8+ T cells, TLRs, and cytokines in the mice's blood, suggesting that chitosan-PEG-PEI may be a promising carrier for in vivo IL-7 gene expression and enhanced innate and adaptive immunity for the prevention of animal diseases.

Biomedical Application of Chitosan and Chitosan Derivatives: A Comprehensive Review.

Chitosan (CS) is a widely known naturally occurring polysaccharide made of chitin. The Low solubility of chitosan in water restricts its use in medical applications. However, several chemical modifications have made chitosan superior in solubility, biocompatibility, biodegradability, stability, and easy functionalization ability. All these favourable properties have increased chitosan's application in drug delivery and biomedical fields. Chitosan-based nanoparticles or biodegradable controlled-release systems are of great interest to scientists. Layer -by-layer technique is employed to develop hybrid chitosan composites. Such modified chitosan is widely used in wound healing and several tissue engineering approaches. This review brings together the potential of chitosan and its modified form in biomedical applications.

Anti-COVID-19 Credentials of Chitosan Composites and Derivatives: Future Scope?

Chitosan derivatives and composites are the next generation polymers for biomedical applications. With their humble origins from the second most abundant naturally available polymer chitin, chitosan is currently one of the most promising polymer systems, with wide biological applications. This current review gives a bird's eye view of the antimicrobial applications of chitosan composites and derivatives. The antiviral activity and the mechanisms behind the inhibitory activity of these components have been reviewed. Specifically, the anti-COVID-19 aspects of chitosan composites and their derivatives have been compiled from the existing scattered reports and presented. Defeating COVID-19 is the battle of this century, and the chitosan derivative-based combat strategies naturally become very attractive. The challenges ahead and future recommendations have been addressed.

Chitosan Derivatives as Carriers for Drug Delivery and Biomedical Applications.

Over the past few decades, chitosan (CS) has gained the attention of researchers investigating newer biomaterial-based carriers for drugs in pharmaceutical and biomedical research. Combined with its nontoxic behavior, biodegradability, and biocompatibility, chitosan has found widespread applications in the fields of drug delivery, tissue engineering, and cosmetics. As a novel drug carrier, chitosan is regarded as one of the promising biomaterials in the pharmaceutical industry. The extensive use of this cationic biopolysaccharide in the delivery of therapeutic agents has brought a few limitations of chitosan into the limelight. Various chemical modifications of chitosan can minimize these limitations and improve the efficacy of chitosan as a drug carrier. The effectiveness of several chemically modified chitosan derivatives, including trimethyl chitosan, thiolated chitosan, PEGylated chitosan, and other chitosan derivatives, has been investigated by many researchers for the controlled and target specific delivery of therapeutics. The chemically modified chitosan derivatives exhibited greater importance in the current scenario on drug delivery due to their solubility in wide range of media along with their interaction with pharmaceutically active ingredients. Chitosan derivatives have also attracted attention in several biomedical fields, including wound healing, hyperthermia therapy, tissue engineering, and bioadhesives. The present review narrates the sources and common physicochemical properties of chitosan, including several important synthetic modifications to obtain chemically modified chitosans and their applications in target-specific drug delivery, along with several biomedical applications.

Exploring the biomedical potential of a novel modified glass ionomer cement against the pandrug-resistant oral pathogen Candida albicans SYN-01.

Dental caries is an infectious disease that is a major concern for dentists. Streptococci and Lactobacilli were long thought to be the primary etiology responsible for caries. Candida albicans with acidogenic and aciduric characteristics has recently been implicated in the onset and progression of cariogenic lesions. Moreover, due to the increased resistance to common antimicrobials, the discovery of innovative candidates is in high demand. Therefore, our study might be the first report that explores the efficacy of glass ionomer cement (GIC) incorporated with a newly modified carboxylated chitosan derivative (CS-MC) against multidrug-resistant (MDR) and/or pandrug resistant (PDR) C. albicans isolated from the oral cavity. In this work, four CS-MC-GIC groups with different concentrations were formulated. Group four (CS-MC-GIC-4) gave a significant performance as an anticandidal agent against selected PDR Candida strain, with an obvious decrease in its cell viability and high antibiofilm activity. It also, enhanced all the mechanical properties and supports cell viability of Vero cells as a nontoxic compound. Moreover, CS-MC-GIC-4 inhibited neuraminidases completely, which might provide a novel mechanism to prevent dental/oral infections. Thus, findings in this study open up new prospect of the utilization of CS-MC-GIC as a novel dental filling material against oral drug-resistant Candida.