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. 2023 Feb 28;15(3):647. doi: 10.3390/v15030647

Table 2.

CS derivatives applied as antivirals or antiviral carriers, with properties and preparations.

CS Derivatives Formula Physical Properties Biological Properties Preparation Method Advantages/Limitations/Potential Uses References
Ionic Derivatives
Quarternized derivatives graphic file with name viruses-15-00647-i028.jpg -cationic derivatives
-water-soluble at neutral pH
-N,N, N-trimethyl CS chloride (TMC) ↑ aqueous solubility than CS
-biocompatibility
-biodegradability
-mucoadhesion
-direct quaternary ammonium substitution
-epoxy derivative open loop
-N-alkylation
-antifungal, antibacterial, antituberculosis
-enzyme inhibition
-permeation enhancers
-gene transfection and delivery
-good moisture retention and absorption
-mucoadhesivity ↓ with ↑ degree of quaternization
-↑ degree of quaternization ↓ intrinsic viscosity
-pH 7.4 CS and salts failed to increase the permeability
-absorption enhancer for intestinal lumen with pH close to its pKa
-TMC collects and delivers more negatively charged DNA/genes
than plain CS
-quaternized CS ↑ hydroxyl radical scavenging activity in comparison to other CS
-pH-sensitive targeting
[184]
Sulfated derivatives graphic file with name viruses-15-00647-i029.jpg -water-soluble sulfoethylated CS with improved swelling property
-during sulfation, some amino groups of CS are converted to anionic centers, which leads to better polyelectrolyte properties
-N-alkyl-O-sulfated CS has
amphiphilicity since it carries long-chain alkyl groups with a hydrophobic nature and sulfated groups with a hydrophilic
nature
-biocompatibility
-biodegradability
-sulfation of
2-chloroethane sulfonic acid sodium salt in alkaline media
-sulfur-containing derivatives were obtained by reacting CS
with CS2, formaldehyde, and primary amine
-antisclerotic, antioxidant, antibacterial, anti-HIV, antiviral, and enzyme inhibition
-blood anticoagulant
-hemagglutination inhibition activity
-amphiphilic polymer enables the formation of micelles with physical entrapment of water-insoluble drugs such as taxol
-structural similarity of CS salt with heparin
-high sorption capacities
-a great advantage for metal ion recovery
[25]
CS derivatives with sugar part graphic file with name viruses-15-00647-i030.jpg -water-soluble
-investigated
mainly for rheological studies
-biodegradability
-biocompatibility
-nontoxic
-reductive N-alkylation (using NaCNBH3 and unmodified sugar, a sugar-aldehyde derivative, or N-alkylation of CS performed
in aqueous methanol with various aldehydes,
monosaccharides, and disaccharides)
-antibacterial and antimicrobial activity
-this type of modification has usually been used to introduce cell-specific sugars into CS
-synthesis of sugar-bound CS, such as
those with D- and L-fucose, and their specific interactions with lectin and cells
-lactose-modified CS for a potential
application in the repair of the articular cartilage
-galactosylated CS prepared from lactobionic acid
and CS with 1-ethyl-3-(3-dimethyl aminopropyl)-
carbodiimide (EDC) and N-hydroxysuccinimide (NHS)
showed promise as a synthetic extracellular matrix for hepatocyte
attachment
-graft copolymers of galactosylated CS with poly(ethylene glycol) or poly(vinyl pyrrolidone) were useful as hepatocyte-targeting DNA carriers
[181,185,186]
CS glutaraldehyde crosslinked polymer graphic file with name viruses-15-00647-i031.jpg -improved permeability, mechanical properties, wetting, and chemical resistance
-gelation temperature: 32–33 °C
-viscosity of the hydrogel increased quickly after gelation
-not cytotoxic to human corneal epithelial cells at a low concentration
-biocompatibility
-biodegradability
-CS dissolved in acetic acid with glutaraldehyde performed in a short time -N-trimethylated CS crosslinked
with glutaraldehyde has been used to fabricate hollow
microspheres for drug loading
[187]
CS cyclodextrin derivatives graphic file with name viruses-15-00647-i032.jpg -can enhance the solubility of sulfadiazine, sulfamonomethoxine, and sulfamethoxazole -antimicrobial activity
-antifungal activity
-bioavailability
-nontoxic
-biodegradability
-physical mixing, kneading, co-precipitation, and solvent evaporation -increases dissolution
-improves stability
[188,189,190]
CS oligomers graphic file with name viruses-15-00647-i033.jpg -soluble over a wide pH range, from acidic to basic
-water-soluble
-antioxidant activity
-anti-inflammatory activity
-antiviral activity
-nontoxic
-antifungal activity
-biodegradability
-biocompatibility
-immunological and antibacterial activities
-prepared from the degradation of CS
-oxidative degradation method involving hydrogen peroxide (H2O2) and combined degradation using hydrogen peroxide and microwave radiation
-inhibit the expression of TNF-α, IL-6, and iNOS, which are associated with an inflammatory response
-depress oxidative stress
-decrease induced cell apoptosis
-alleviate or delay Alzheimer´s disease process
[191,192]

↑ means increase, ↓ means decrease.