The mono carboxylated dextran (Mono COOH-Dextran) is a versatile and promising biopolymer for the delivery of drugs because of its chemical properties and biocompatibility. Made from dextran, a long-chained polysaccharide made of glucose molecules, Mono COOH-Dextran is created by adding one carboxyl atom per dextran molecule. This functionalization greatly improves its solubility and reactivity, which makes it a perfect candidate for conjugation with several therapeutics. Because the carboxyl group is arranged so precisely, the drug attachment and release can be controlled in a very specific and efficient manner. In contrast to the unprocessed version, Mono COOH-Dextran has enhanced interaction with drug molecules and biological tissues – solving some of the major bottlenecks in contemporary drug delivery.
Figure 1. Illustration of the dextran decoration with guanosine mono-substituted benzene-1,4-diboronic acid moieties and subsequent self-assembly in the presence of K + into DGH hydrogels.( Sardaru MC, et al.; 2023)
What's remarkable about Mono COOH-Dextran is that it forms stable complexes with various drugs ranging from small molecules to proteins to nucleic acids. Carboxyl group as covalent binding site with amine-based drugs via amide linkage. This chemical coupling holds the drug permanently glued to the dextran backbone until it arrives at the target where environmental conditions or enzymatic activity could permit controlled release. This is a great feature for chemotherapy, which works by aiming to directly attack the cancer cells, with as little harm to healthy tissue as possible. Several experiments have demonstrated that Mono COOH-Dextran conjugates can make hydrophobic drugs more soluble and stable, bioavailable and less toxic to the body. Furthermore, the controlled release allows the medication to remain at therapeutic levels for longer and thus enhances treatment efficacy. Its biocompatibility and biodegradability also lends Mono COOH-Dextran an appeal in drug delivery. Mono COOH-Dextran is derived from dextran and is safe and immunogenic to the extent that it is easily absorbed by the body and converted into benign byproducts by the natural metabolism. It is therefore ideal for all modes of administration such as oral, intravenous, and transdermal. What's more, the specificity of Mono COOH-Dextran is what allows multi-functional drug delivery. For example, it can be crafted into nanoparticles, hydrogels or micelles that could bind drugs, guard them from degradation, and deliver them specifically. This carboxyl group also makes it possible to add further targeting ligands (eg, antibodies or peptides) to the carrier directing the drug-loaded particle to the cells or tissues. This targeting potential not only increases the drugs' therapeutic index but it also lowers the risk of adverse effects.
When used for targeted drug delivery, the versatility of Mono COOH-Dextran doesn't just stop at a drug carrier. The carboxyl bond can be conjugated to imaging agents to create theranostic platforms for both therapy and diagnostic applications. These platforms monitor the drug movement and release in real-time, which can inform the treatment effectiveness and allow for adjustment at an early stage. It also enables conjugation to other biomolecules which makes Mono COOH-Dextran an attractive material for tailor-made medicine strategies. If you can tailor the drug delivery system to each individual patient, you can get better, customized therapies. For instance, for cancer, Mono COOH-Dextran can be paired with antibodies that recognize tumor markers, and then the drug is directed to the cancer cells so that healthy tissues are not affected.Nor is Mono COOH-Dextran only useful for conventional applications in drug delivery. it's also been very promising in gene therapy – to deliver nucleic acids like DNA, RNA or small interfering RNA (siRNA). Because the carboxyl group is reactive, it can form stable complexes with these genes to keep them from degrading and thereby increase their uptake by cells. This is an essential property for gene therapy to work – because it's the one that helps ensure that the therapeutic genes can get to their target cells and do what they're meant to do. Mono COOH-Dextran-derived vectors could be used to release siRNA to knock down specific disease-causing genes and could be used to treat genetic disease and cancer. Further, Mono COOH-Dextran's hydrogeling properties also make it possible to deliver controlled and extended doping of drugs. Hydrogels are 3-D polymer networks that can hold enormous amounts of water while being extremely strong. As a drug delivery medium, Mono COOH-Dextran hydrogels will encapsulate drugs and release them over time as they're in physiological response. This sustained release technique is especially advantageous for diseases requiring long-term treatment because it reduces time to take the drug and increases patient compliance. Also, due to the hydrogel's biocompatibility, there is very little tissue irritation or toxicity and therefore suitable for various biomedical applications such as wound therapy and tissue engineering. A second impressive use for Mono COOH-Dextran is as a vaccine agent. Conjugation of antigens with Mono COOH-Dextran can augment the immune system by stabilizing the antigen and making it available to the immune system. Such a technique can increase the efficiency of vaccines, especially those based on protein or peptide antigens, which tend to be highly susceptible to degradation. In the case that the antigens are maintained intact and can reach the target immune cells in the right way, Mono COOH-Dextran conjugates can trigger a stronger and more durable immune response and be more effective against infectious diseases.
Alternate Names:
Mono-carboxylated dextran, 70 kDa
70 kDa Carboxy-Dextran
Mono-COOH dextran
70 kDa carboxymethylated dextran
Carboxy-dextran (70 kDa)
Dextran-COOH, 70 kDa
Mono-carboxyl dextran (70 kDa)
References:
1. Sardaru MC, et al.; Dynameric G-quadruplex-dextran hydrogels for cell growth applications. Chem Commun (Camb) . 2023, 59(21):3134-3137.
Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery
J Cell Physiol.
Authors: Zahiri M, Babaei M, Abnous K, Taghdisi SM, Ramezani M, Alibolandi M.
Abstract
In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.
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