Dextran-Azide or Dextran-N3: This modified polysaccharide is made by reacting an azidating agent with dextran. And Dextran is a chemical structure that's 2 to 10 glucose molecules attached together by glycosidic bonds. Azide-modified dextran is water soluble and biocompatible so it's commonly used in biomaterials and nanoparticle carriers. Moreover, it is obtained by reacting with an azidating agent and biocompatible and degradable which can be used for the drug delivery use. Dextran-azide can be provided in different molecular weight, common molecular weight are 4k, 10k, 20k, 30k, 50k, 60k, 70k etc. it's flat or pale foamy, the shape depending on its molecular mass. Moreover, it is easily dissociated in the majority of organic solvents (DCM), N, N-dimethylformamide (DMF), DMSO and tetrahydrofuran (THF). If you marry the virtues of dextran – low toxicity and good water solubility – with the flexibility of the azide group, then dextran-N3 provides an all-purpose starting point for developing drug delivery systems.
Figure 1. Synthesis route for the modification of dextran. (Bitsch P, et al.; 2023)
The coolest part about Dextran-N3 is the click chemistry it has, especially with alkynes. Because the azide group exists, dextran azide will click chemistry with alkynes under copper-catalysed conditions. This biocompatible reaction can take place under benign circumstances, which keeps delicate biomolecules like proteins and nucleic acids intact. Dextran-N3 is a powerful targeted drug delivery system because it is selectively and effectively attached to therapeutic molecules. By binding to tumor marker-specific targeting ligands, for instance, dextran-N3 can trigger chemotherapeutic agent engulfment directly into cancer cells. This selective intervention can reduce the systemic adverse events found in traditional therapies and thus enhance patient care and quality of life. Apart from being highly targeted, Dextran-N3's hydrophilicity also boosts its pharmacokinetics. It facilitates a longer time for the blood to circulate the drug that is critical to a proper level of the drug at the target site of action. The extended circulation helps not only to deliver drugs more effectively, but also to lower the rate of dosing, which helps patients stick to treatment protocols. Furthermore, dextran-N3 is biocompatible and does not cause an immunogenic response, thereby increasing its clinical utility. Modifiability of dextran-N3 is another major plus. Scientists can control how much azide group is substituted — this will affect different aspects like drug loading capacity and release rate. This customization allows sustained-release medications that release drugs slowly over time. These are especially useful in chronic diseases, that need to be given regularly. Sustained release could, for instance, maintain a drug's efficacy levels in cancer therapy, perhaps increasing treatment efficacy and toxicity. Moreover, not only can dextran-N3 be conjugated with the conventional small molecule drugs, but also a number of bioactive molecules like peptides, proteins and even nucleic acids. This ubiquity allows advanced therapies, including gene therapy vectors carrying RNA or DNA payloads. The fact that it is stable in complex with nucleic acids and not easily broken-down renders dextran-N3 a promising candidate for gene delivery. That is especially relevant in personalized medicine, where individualised therapy approaches are becoming more prevalent. Combining dextran-N3 with nanotechnology adds a further layer of flexibility for drug delivery. Using nanoparticles coated with dextran-N3 to coat the drugs can harness the power of dextran polymers and nanocarriers. The mixture can increase hydrophobic drugs' solubility, cell absorption and controlled release profile. The nanoparticles made of Dextran-N3 can even be configured to react to environmental factors, such as pH or temperature, so that they can be used to inject drugs on demand, in particular environments. Such a control is especially useful when it comes to disease sites like tumors that can have a unique microenvironment relative to normal tissues. Dextran azide can be click chemistry conjugated to other molecules to produce selective delivery of drug.
Dextran-N3 has a natural source and safety record. We've seen dextran in a wide variety of medical uses (such as as a plasma expander and for wound repair), so there is solid scientific support for Dextran-N3 drug delivery. Products derived from Dextran-N3 might be more efficiently regulatory than synthetic platforms, meaning quicker time from bench to bedside. Moreover, research on Dextran-N3 in the delivery of drugs is constantly finding new applications and mechanisms of action. It is being tested for its application in immunotherapy, for instance, to zap immune cells with immunomodulators to boost the body's ability to fight tumours. This novel treatment further demonstrates that Dextran-N3 is versatile beyond the drug delivery system, and could be used in a therapeutic future.
Alternate Names:
Azido-Dextran
Dextran Azide Derivative
Azide-Functionalized Dextran
Dextran with Azide Groups
Dextran-N3
Azidoethyl Dextran
Dextran Modified with Azide
References:
1. Bitsch P, et al.; Penetration of Nanobody-Dextran Polymer Conjugates through Tumor Spheroids. Pharmaceutics. 2023, 15(10):2374.
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