Glycol chitosan is a new biopolymer in drug delivery made by chemically altering chitosan, a natural polysaccharide extracted from crustacean exoskeleton. This modification is a change that adds glycol groups to chitosan, making it more soluble in water and more biocompactible and biodegradable. Glycol chitosan has been of particular interest to researchers for its applications in drug delivery because of its special physicochemical features (its nanoparticulate-like structure, its mucoadhesive effects, and the fact that it can be altered with different functional groups). All these make glycol chitosan a desirable carrier for therapeutic molecules, from small molecules to proteins and nucleic acids with superior delivery and targeted delivery. The most prominent use for glycol chitosan in delivering drugs is to create nanoparticles by self-synthesis. It is nanoparticles in this context that make the delivery of a drug more soluble, stable, and bioavailable (especially those that are ineffectively soluble in water). Glycol chitosan nanoparticles can seal many different drugs to ensure they don't degrade or release them unintentionally at the injection site. It's a formulation that enhances the drugs' therapeutic activity by providing a sustained release profile, reducing the number of times that the drugs are taken and preventing toxicities associated with high levels of the drugs. Even better, the nanoparticles can be designed to have a particular size and surface texture that can affect their biodistribution and cellular absorption, making them even more targeting effective. What's more, glycol chitosan is mucoadhesive and thus a great candidate to deliver drugs through mucosal tissues (GI tract, nasal cavity, lungs). Because glycol chitosan is mucoadhesive, it sticks to the skin so the drug can be able to dwell longer and be more easily absorbed. This is especially helpful for drug delivery via the mouth where the harsh environment of the gastrointestinal system can degrade medications before they can be delivered. Glycol chitosan can guard the drug from stomach acid and digestive enzyme activity so that the drug gets to the circulatory system in an increased amount. Glycol chitosan can be further reconstructed chemically, too. Conjugation, for instance, with targeting ligands (antibodies, peptides, etc.) can make drug delivery more targeted to specific cells or tissues (cancer cells, for instance, or inflammation). These changes can be used to enable personalized medicine methods, in which medications are personalised to the patient's particular disease.
Glycol chitosan's self-assembly into nanoparticles is a fundamental part of its use in drug delivery. Nanoparticles facilitate the delivery of medicines by offering a barrier material that can protect medicines from premature breakdown, release, and targettisation to tissues or cells. The advantage of glycol chitosan nanoparticles is that it can be used to contain various therapeutic molecules including hydrophilic and hydrophobic drugs, proteins and nucleic acids. The encapsulation usually involves glycol chitosan molecules self-assembling in water to make nanoparticles by hydrophobic and hydrogen bonding. The particle size and surface roughness of glycol chitosan nanoparticles can be controlled by modifying the state of the self-assembler process: glycol chitosan concentration, solution pH and crosslinking. This is important control because the size and surface charge of nanoparticles determine how much is biodistributed, taken up by cells and eliminated from the body. Nanoparticles between the ages of 50-200nm, for example, are generally considered the most efficient nanoparticles for passive cancer-targeting by EPR (enhanced permeability and retention), with tumor leukocyte vasculature that allows nanoparticles to get trapped faster than in the surrounding tissue. Even more surface modifications, like PEGylation (responsibility of polyethylene glycol chains to each other) can prolong the stability and duration of circulating glycol chitosan nanoparticles by preventing them from being recognized by the immune system. Glycol chitosan nanoparticles also provide a route to targeting drugs via functionalization with ligands. Attaching targeting molecules like antibodies, peptides or small molecules to the surface of the nanoparticles lets scientists target the drug-laden nanoparticles to cells or tissues. The drug is more effective with such targeted delivery, because the drug is delivered at higher levels to the target of action without excess off-target and systemic toxicity. In cancer therapy, for instance, glycol chitosan nanoparticles can be labelled with antibodies to tumor antigens, and the chemotherapeutics can be infused directly into cancer cells without affecting normal ones. This specificity is critical in treating aggressive and metastatic cancers, where chemotherapy can be toxic because it is not selective. Glycol chitosan's mucoadhesiveness means that it is a great candidate for drug delivery through the mucosal tissues (the primary access point for most drugs in the body). Because glycol chitosan adheres to mucosal surfaces, the drug delivery system has more time to dwell at the dose location and the drug will be more readily absorbed and bioavailable. This is especially useful in oral drug delivery, which must pass through the grueling confines of the gut before they enter systemic circulation. It is the mucoadhesive properties of glycol chitosan that save the drug from gastric acid and digestive enzyme degradation so that more of the drug gets to the intestines and in the bloodstream. Besides oral administration, glycol chitosan is ideal for nasal and pulmonary administration, where the mucosal surface of the nose and lungs offer direct access to circulatory system. The nasal route is especially attractive for drug delivery that is poorly absorbed through the gastrointestinal tract or destroyed by first-pass metabolism in the liver. Nanoparticles of glycol chitosan will adhere to the nasal mucosa, which will release the capsuled drug over the mucosal barrier and into the bloodstream. It's a less invasive approach to intravenous administration, which can have an immediate response and a greater patient compliance. Likewise, in the lung, glycol chitosan may help to deposit and maintain inhaled drugs on the epithelium of the lungs for better local and systemic delivery of agents that treat respiratory conditions including asthma, COPD and lung cancer. Structural alterations of glycol chitosan can increase its mucoadhesive and delivery capability. By adding thiol groups to glycol chitosan, for instance, we can make it stronger against mucoadhesion, by binding disulfide residues with cysteines in the mucus gel. Such more powerful interactions extend the duration of the drug delivery system's stay at the mucosal surface, which increases absorption and bioavailability of the drug. Conjugation with targeting ligands also allow more specific delivery to specific cells or tissues in the mucosal tissue. Glycol chitosan nanoparticles, for example, can be modified with lectins that recognize particular carbohydrate moiety in epithelial cells' surface and deliver targeted drug to the cells.
Because glycol chitosan is versatile and specific, many different therapeutic applications use it in drug delivery systems. Researchers are still trying to perfect glycol chitosan preparations for many conditions, from cancer and infectious disease to chronic inflammatory conditions and neurodegenerative disorders. Control of the shape, surface and function of glycol chitosan nanoparticles opens the door to personalised drug delivery platforms to overcome biological barriers and deliver drugs more effectively. For example, in the treatment of cancer, glycol chitosan nanoparticles have delivered many chemotherapy drugs including doxorubicin, paclitaxel and cisplatin. Such nanoparticles could be reconfigured and passively targeted by EPR effect or active targeted by ligand conjugation to inject drugs with enhanced therapeutic activity and less severe systemic side effects. You could even inject glycol chitosan for combinations therapies — many drugs within the same nanoparticle to work together for a better patient experience. Particularly valuable in the battle against drug resistance, one of the major challenges of treatment for cancer, by giving people many differents drugs that affect to signaling pathways involved in the survival and proliferation of cancer cells. In use for infectious diseases, the glycol chitosan nanoparticles can carry antibiotics, antivirals and antifungals in a more stable, bioavailable and penetration into infected tissue. Antibiotic-loaded nanoparticles of glycol chitosan, for example, might be made to target bacteria biofilms that can't be neutralized by the regular antibiotics. Glycosan's mucoadhesive properties can also permit the antiviral drugs to penetrate mucosal tissues such as the respiratory and gastrointestinal tracts from which viral infection generally emerges. And then there are glycol chitosan drug delivery systems being evaluated for chronic inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease (IBD).
Alternate Names:
Chitosan glycolate
Glycol-modified chitosan
Chitosan glycol conjugate
Chitosan glycol derivative
O-glycol chitosan
Glycolated chitosan
Glycol-chitosan complex
Chitosan-glycol ester
References:
1. Saboktakin MR, et al.; Synthesis and characterization of pH-dependent glycol chitosan and dextran sulfate nanoparticles for effective brain cancer treatment. Int J Biol Macromol. 2011, 49(4):747-51.
Tumor-Targeting Glycol Chitosan Nanoparticles for Cancer Heterogeneity
Adv Mater.
Authors: Ryu JH, Yoon HY, Sun IC, Kwon IC, Kim K.
Abstract
Nanomedicine is extensively employed for cancer treatment owing to its unique advantages over conventional drugs and imaging agents. This increased attention to nanomedicine, however, has not fully translated into clinical utilization and patient benefits due to issues associated with reticuloendothelial system clearance, tumor heterogeneity, and complexity of the tumor microenvironment. To address these challenges, efforts are being made to modify the design of nanomedicines, including optimization of their physiochemical properties, active targeting, and response to stimuli, but these studies are often performed independently. Combining favorable nanomedicine designs from individual studies may improve therapeutic outcomes, but, this is difficult to achieve as the effects of different designs are interconnected and often conflicting. Glycol chitosan nanoparticles (CNPs) are shown to accumulate in tumors, suggesting that this type of nanoparticle may constitute a good basis for the additional modification of nanoparticles. Here, multifunctional glycol CNPs designed to overcome multiple obstacles to their use are described and key factors influencing in vivo targeted delivery, targeting strategies, and interesting stimulus-responsive designs for improving cancer nanomedicine are discussed.
Datasheet
