Chitosan derivatives for pharmaceutical applications

Chitosan, obtained by alkaline deacetylation of chitin and its various semisynthetic derivatives, have been attracting much attention due to its natural origin, abundance and low cost. Chitosan derivatives like Chitosan Diacetate and Chitosan Triacetate is commonly used in pharmaceutical applications.  

Chitosan and its Properties

Chitosan (CS) is considered a nontoxic biodegradable  polysaccharide that is derived from alkaline deacetylation of chitin, which forms the exoskeleton of insects and other crustacean, this polysaccharide mainly consists of repeating units of glucosamine and N-acetyl-glucosamine, and known to be insoluble at neutral pH but soluble and positively charged at acidic pH, interestingly  chitosan has gained attention as a biocompatible matrix for drug controlled release and has been the subject of numerous studies in the last decades as Positively charged forms of  chitosan will bind to cell membranes and is reported to decrease the trans-epithelial electrical resistance (TEER) of cell monolayers as well as to increase paracellular permeability.

Mechanism of permeation enhancements

The mechanism of enhancing the permeation is mediated by the positive charges on the chitosan, which includes interactions with the tight junction proteins as occludin and ZO-1, redistribution of F-actin, and slight destabilization of the plasma membrane  which will allow  to enhance absorption byincreasing cellular permeability,  and that have been a major factor contributing to its widespread evaluation as a component of oral dosage forms.

Chitosan Modification and derivatives

CS has beenregarded as a source of potential bioactive material, but it also has several limitations to be utilized in biological system, including its poor solubility under physiological conditions. Therefore, to overcome these limitations the light was focused on the derivatization of CS , and the main factors which mayaffect  its properties are its molecular weight and degree of deacetylation (DD). These factors enable the researcher to formulate different grades of Chitosan which differ primarily in molecular weight and degree of deacetylation during the processing from row material, so they used different conditions such as type and concentration of reagents and temperature employed which can affect the physical properties of the product which in terms affects  viscosity, solubility and elasticity.

Chemical modification

Chemical modification of chitosan that is achieved by altering the functional groups in a compound and that can be done by several ways which include: radiation, chemical, photochemical, plasma-induced and enzymatic grafting methods results in the formation of several derivatives such as quaternized chitosan, thiolated chitosan, carboxylated chitosan, amphiphilic chitosan and of the interesting examples is the  Lactose modification of the chitosan backbone (1-deoxylactit-1-yl chitosan) that has been used in combination with the polyvalent ion tripolyphosphate to form colloidal coacervates though poly-ionic interactions, forming highly uniform and small (200 nm diameter) nanoparticles.

Physical modification

Physical modification of chitosan derivatives is achieved by blending, which involves the mixing of two or more polymers physically, an example of physical modification in controlled drug delivery is represented by amoxicillin formulated with a crosslinked chitosan/PVP blend with glutaraldehyde to form a semi-interpenetrating polymer (semi-IPN).

So by modifying the chemical functional groups that Chitosan has, that would achieve specific goals, making it a polymer with a stupendous range of potential applications and making it as a carrier in polymeric nanoparticles for drug delivery through various routes of administration.

Chitosan Nanoparticles

chitosan-derivatives can be formulated as nanoparticles that centres a tunable drug release and impact the pharmacokinetic profile of the loaded drug, and there are several mechanisms that explain the drug release from chitosan nanoparticles such as: swelling of the polymer, drug diffusion through the polymeric matrix, diffusion of the adsorbed drug, polymer erosion or degradation and a combination of both erosion and degradation.

Innovative Chitosan diacetate and Chitosan triacetate Nano particulate drug delivery systems can efficiently encapsulate anticancer drugs especially those of favourable physicochemical properties, water soluble and ionized into positively charged species. Encapsulation of drugs in chitosan derivatives nanoparticles enhanced their cellular accumulation through several mechanisms including modulation p-gp efflux transporters..