Dextran is a branched glucan made up of glucose molecules that is biocompatible, biodegradable and chemically multifunctional. When functionalised with amines, dextran-amine can be used as an incredibly effective carrier for a host of therapeutics, with distinct advantages for stability, controlled release and selective delivery. Its many purposes and advantages as a carrier material are what highlight the uses of dextran amine for drug delivery. Dextran amine comes from dextran. Therefore it also shares the high biocompatibility, biodegradability and non-toxicity of dextran and is already being extensively researched for drug delivery. Furthermore, dextran can be fabricated into various derivatives through chemical chemistry (click synthesis chemistry) that can self-assemble into drug-filled nanoparticles in aqueous solution for efficient drug encapsulation and delivery.
Figure 1. Reaction scheme and structure of resulting dextran amino acid esters. (Konrad Hotzel, et al.; 2019)
Dextran-amine is produced by adding amine groups to the dextran backbone and this produces a modified polymer with the intrinsic properties of dextran and the reactivity of amine functions. This modification makes dextran much more solubile and stable in water, which is an attractive biomedical candidate. The amines on dextran-amine make it possible to conjugate almost any kind of drug, from small molecule chemotherapeutics to giant biomolecules such as proteins and nucleic acids. This plethora comes from amine groups having stable covalent bonds with carboxyl, aldehyde, and other reactive groups found in therapeutic agents that provide the effective loading and storage of drugs. Among the most significant benefits of dextran-amine, nanoparticles and hydrogels can be created using it that make great drug delivery systems. Nanoparticles based on dextran-amine can be used to encapsulate the drugs within their shell or attach them to the shell, which acts as a shield against the drugs from early degradation and makes them more bioavailable. Also, these nanoparticles can be designed to have surface effects that would allow them to be targeted at specific tissues or cells with minimal off-target and systemic toxicity. The hydrogels from dextran-amine, however, provide a platform for localised and long-term drug delivery and can be used in applications where long-term therapy is required, like in chronic disease or wound healing.
Applications for dextran-amine in the delivery of drugs are diverse and are growing as more work in this area occurs. It is one application in cancer care, for example, where dextran-amine-based drug delivery systems have been extremely promising for the efficacy of chemotherapy. By binding anticancer drugs to dextran-amine, researchers have made nanocarriers that bind only to tumor cells and spare normal tissue, which eliminates the side effects that come with chemotherapy. Further, the localised drug delivery of dextran-amine hydrogels has also been shown to enhance the treatment success of solid tumor therapies because the hydrogels can deliver a sustained flow of drugs at the tumor. The second promising application for dextran-amine is in the delivery of genetic material for gene therapy. The amines on dextran-amine can be stabilized to nucleic acids, where they can withstand enzyme reactions and reach the target cells. This ability has been used to engineer non-viral vectors for gene delivery that are safer than virus vectors. Further, dextran-amine is biocompatible and immunogenic (i.e., less toxic) than many others, which is useful for in vivo applications where immune reactions to the delivery system might otherwise undermine the therapeutic benefit. Polymer chemistry and nanotechnology could still improve the properties and applications of dextran-amine to allow for more effective, high-performance drug delivery systems. By including stimuli-responsive components in dextran-amine nanoparticles, for example, the release of drugs can be controlled to certain physiological signals, like pH or temperature. That would add yet another dimension of accuracy in drug delivery so that agents that cure are administered are released only where they are needed. This lends dextran its promise for use as an anti-tumor agent. Moreover, dextran can also be bonded to bioactive drugs in the form of prodrugs that can be directed to target and stabilise drugs via direct linking or spacer arm tethering. They also coat and engulf the cell with hydrophobic drugs and hydrophilic molecules through Dextran vesicles. Dextran vesicle scaffolds have been found to enhance the stability and cellular absorbability of drugs, and thus the therapeutic efficacy. Besides that, dextran can also be targeted via targeted recognition of receptors on the surface of immune cells. The -glucan profile on yeast microcapsules, for instance, can be identified by immune cells to get loaded drugs to the lesion site and help target and deliver drugs better.
Alternate Names:
Amino-dextran
Dextran amine
Dextran with amino groups
Amino-modified dextran
Dextran-NH₂ conjugate
Aminated dextran
Dextran amine derivative
References:
1. Konrad Hotzel, et al.; Protonation behavior of dextran amino acid esters. Turkish Journal of Chemistry. 2019, 43(3):869-880
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