Chitosan, as a natural polysaccharide, has received extensive attention and has been used to prepare nanoparticles. Chitosan is a linear polysaccharide obtained by deacetylation of chitin, consisting of β-(1-4)-d-glucosamine and N-acetylglucosamine. Its average relative molecular mass ranges from 50×103 to 2000×103. Chitin and chitosan can be obtained from shellfish sources such as crabs, shrimps, krill, insects and fungi. Chitosan is a non-toxic, biocompatible material that shows a wide range of potential applications, especially in the biomedical field.
Figure 1. Chemical Structure and some sources of chitin and chitosan.(Ibrahim MA, et al. 2023)
Chitosan contains 3 types of reactive groups (1 amino group and 2 hydroxyl groups), in which the primary and secondary hydroxyl groups are located in repeating glycoside units respectively. The presence of these functional groups, chitosan modified by chemical groups has provided many useful materials for food, cosmetics, and biomedical and pharmaceutical applications. Chemically modified chitin and chitosan structures are obtained by generating free radicals on the chitosan chain, which react with polymerizable monomers and produce grafted chains. In addition, the increased charge density after ionization of amino groups makes chitosan suitable for chemical reactions such as alkylation, acylation, and carboxymethylation. Quaternization of the amino groups makes chitosan a cationic polyelectrolyte with a pKa of approximately 6.5. At low pH, the amino group is protonated and becomes positively charged. Its polycationic surface makes chitosan suitable for adhesion to negatively charged matrices, aggregation of polyanionic compounds, and chelation of different metal ions such as Ca2+, Ba2+, and Al3+. Based on its biocompatibility, biodegradability, bioadhesion, bioactivity, and low toxicity, chitosan has been widely used as a system for cell proliferation, tissue engineering, targeted drug delivery, and pharmaceutical excipients in the biomedical field. Due to their excellent biocompatibility and biodegradability, polysaccharides (such as chitosan and dextran) are often considered as ideal candidates for the design and fabrication of micro- and nanoparticles in the fields of medicine and biotechnology. In addition, chitosan contains abundant amino groups and is an ideal material for preparing pH-responsive microgels. The preparation of polymer-based microgels or nanogels can be carried out through different cross-linking methods, such as chemical cross-linking or physical cross-linking. Chemical cross-linking is to prepare chitosan-based microgel networks by performing covalent cross-linking reactions between functional groups of chitosan (such as amino and hydroxyl groups). Commonly used cross-linking agents include glutaraldehyde, glyoxal, genipin or succinimide end-functionalized polyethylene glycol. Chitosan and glutaraldehyde can form covalent imine bonds through the reaction of the amino group of chitosan with the aldehyde group of glutaraldehyde. Another form of cross-linking agent is genipin, which is an excellent natural cross-linking agent and exhibits excellent cross-linking properties with chitosan, proteins, collagen and gelatin and is also superior to many other synthetic Cross-linking agents have low toxicity. Therefore, it has been widely used in biomedical applications. By chemically modifying chitosan and introducing functional groups to form chitosan derivatives, certain aspects of its characteristics can be further improved to meet research needs. Common chitosan derivatives include acylated chitosan, carboxylated chitosan, alkylated chitosan, quaternized chitosan, etc. Acylated chitosan derivatives: the amino and hydroxyl groups of chitosan can react with a variety of organic acids, acid anhydrides, acid chlorides, etc. to form acylated chitosan derivatives. The introduced groups can weaken the intramolecular neutralization of chitosan. Intermolecular hydrogen bonds improve the water solubility of the derivatives. Acylated chitosan has a wide range of applications. High-solubility acylated chitosan can be used as a drug delivery carrier, while high-crystallinity acylated chitosan has good processability and can enhance the toughness of fibers.
Carboxylated chitosan derivatives have strong mucoadhesion and are often used as mucosal drug delivery carriers, and are widely used in intestinal, nasal mucosa and oral delivery. Alkylated chitosan derivatives: chitosan mainly undergoes alkylation reaction through the amino group to generate N-alkylated derivatives. The hydroxyl group can also participate in alkylation to generate O-alkylated derivatives, which is similar to chitosan. Compared with chitosan, the hydrogen bonds in the alkylated chitosan molecule are significantly weakened, and the water solubility is increased. The introduced long-chain alkyl groups are hydrophobic, so the water solubility of alkylated chitosan derivativescan be controlled by adjusting the introduced alkyl groups. Alkylated chitosan derivatives have better coagulation effects and biocompatibility than chitosan, and their hemostatic properties are affected by the length of the alkyl chain, so they can be used as ideal hemostatic materials. Quaternized chitosan derivatives. Quaternized chitosan is usually a positively charged cationic polymer produced by direct N-substitution of chitosan or reaction with a quaternary epoxide. The alkyl group carried by the quaternary epoxide The groups can make the quaternized chitosan formed have different hydrophilic/hydrophobic properties. Common quaternized chitosan include N, N, N-trimethylchitosan and N, N, N-TrimethylO -(2-hydroxy-3-trimethylammoniumpropyl) chitosan, N-2-hydroxypropyldimethylethylammonium chloride chitosan, etc. Quaternization introduces a large number of positive charges and increases the hydrophilicity of the derivatives, which greatly improves the solubility of quaternized chitosan in neutral and alkaline solutions. Therefore, quaternized chitosan has a wider range of applications and more effective antibacterial properties than unmodified chitosan.
Alternate Names:
Deacetylated chitin
Chitosan oligosaccharide
Chitosan hydrochloride
Chitosan acetate
References:
1. Ibrahim MA, et al. A Review of Chitosan and Chitosan Nanofiber: Preparation, Characterization, and Its Potential Applications. Polymers (Basel). 2023, 15(13):2820.
Chitosan lactate wafer as a platform for the buccal delivery of tizanidine HCl: in vitro and in vivo performance
Int J Pharm
Authors: El-Mahrouk GM, El-Gazayerly ON, Aboelwafa AA, Taha MS.
Abstract
Tizanidine HCl is a skeletal muscle relaxant that suffers from extensive hepatic metabolism resulting in 34-40% oral bioavailability. It also suffers from short half-life (2.1-4.2h) that necessitates frequent administration thus reducing patient compliance. In addition, tizanidine HCl is water soluble, so it is a challenging candidate for controlled drug delivery. In our study, tizanidine was encapsulated in chitosan lactate beads cross-linked with sodium tripolyphosphate. The beads were further incorporated into chitosan lactate wafer to be easily applied to buccal mucosa, aiming to bypass the hepatic metabolism. A central composite face-centered design was applied to statistically optimize the formulation variables; tripolyphosphate concentration, chitosan lactate concentration and polymer/drug ratio. The optimized formula suggested by the software composed of; 3.03% tripolyphosphate, 4.92% chitosan lactate and 2.13 polymer/drug ratio. It provided encapsulation efficiency of 56.5% and controlled tizanidine release over 8h. It is also characterized by being mucoadhesive and nonirritant. Pharmacokinetic parameters of tizanidine from the optimized formula were compared to those of the immediate release tablet, Sirdalud(®), as reference in human volunteers using a randomized crossover design. Significant increase was observed for Tmax and AUC(0-∞). The increase in relative bioavailability of TIZ from the optimized formula was 2.27 fold.
Chitosan lactate as a nonviral gene delivery vector in COS-1 cells
AAPS PharmSciTech
Authors: Weecharangsan W, Opanasopit P, Ngawhirunpat T, Rojanarata T, Apirakaramwong A.
Abstract
The purpose of this research was to evaluate chitosan lactate (CL) of different molecular weights (MWs) as a DNA complexing agent for its efficiency in transfecting COS-1 cells (green monkey fibroblasts) and its effect on cell viability compared with polyethylenimine (PEI), a commercially available cationic polymer. CL and chitosan base dissolved in dilute acetic acid (chitosan acetate [CA]) of different MWs (20, 45, 200, 460 kDa) and N/P ratios (2:1, 4:1, 8:1, 12:1, 24:1) formed complexes with pSV beta-galactosidase plasmid DNA. The complexes were characterized by agarose gel electrophoresis and investigated for their ability to transfect COS-1 cells compared with PEI. Additionally, the effect of CL on the viability of COS-1 cells was investigated using 3-(4,5-dimethyliazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The binding of CL/DNA and CA/DNA was dependent on chitosan MWs. The N/P ratio of CL to completely form the complex with the DNA was higher than that of CA. Both CL and CA were comparable in transfection efficiencies at an N/P ratio of 12:1, but less efficient than PEI (P < .05). The cell viability in the presence of CL and CA at all MWs was over 90%, whereas that of PEI-treated cells was approximately 50%. These results suggest the advantage of CL for in vitro gene transfection, with the ease of preparation of polymer/DNA complexes and low cytotoxicity.
A chitosan lactate/poloxamer 407-based matrix containing Eudragit RS microparticles for vaginal delivery of econazole: design and in vitro evaluation
Drug Dev Ind Pharm
Authors: Parodi B, Russo E, Caviglioli G, Baldassari S, Gaglianone N, Schito AM, Cafaggi S.
Abstract
A matrix based on chitosan lactate and poloxamer 407 was evaluated as a delivery system for the vaginal administration of the antifungal drug econazole. The matrix was investigated both containing the pure drug and after introducing microparticles of Eudragit RS 100 containing econazole. Eudragit RS 100 microparticles were prepared using an emulsion-extraction method and dispersed in a solution containing chitosan lactate (2% w/w) and poloxamer 407 (1.7% w/w). The microparticles, obtained with a yield of 64% w/w and an encapsulation efficiency of 42% w/w, had a diameter of less than 2 μm and a drug loading of 13% w/w. The compressed matrices, characterized by DSC, swelling, erosion, release and mucoadhesion studies, had behaviours dependent on the relative amounts of the contained microparticles. The matrix without microparticles (MECN) showed zero-order release kinetics, with a maximum drug-release of 60% w/w, while those containing 50 or 75% w/w microparticles showed a diffusion controlled release up to 8 and 16 h, respectively, and a linear trend after those time intervals, caused by the erosion process, which allowed reaching a drug-release of approximately 100% w/w at 22 h. In in vitro experiments, the matrices were mucoadhesive and active in inhibiting the growth of Candida albicans 796.
Datasheet
