Dextran is a neutral natural polysaccharide with excellent biosafety. It has been widely used as a plasma substitute in clinical practice. In addition, its molecular structure carries a large number of free hydroxyl groups, which is easy to be chemically modified. It has high application value as a biomaterial. Dextran exists in the mucus secreted by some microorganisms. It is a common natural polymer with excellent biocompatibility, hydrophilicity and low protein adsorption. It can be used as a plasma volume expander and anticoagulant therapeutic drug in clinical practice. In addition, it has many applications in the food, medicine, chemical and other industries, such as excipients, stabilizers, fluxing agents and carriers. Dextran is easy to be chemically modified and can obtain various products through reactions such as reduction and oxidation. Researchers have been studying the use of dextran as a carrier in new polymer drug delivery systems. So far, dextran has been widely used in various DDS such as dextran hydrogels, micelles, core-shell nanoparticles, etc. for targeted drug delivery. Some researchers have reported that supramolecular nanocarriers prepared with dextran have a very high encapsulation rate for doxorubicin. The nanoparticles have excellent monodispersity and stability, can release high doses of DOX in the acidic environment of cancer cell endosomes and lysosomes, and reduce the toxic side effects of doxorubicin.
Figure 1. Applications of dextran and dextran derivatives. (Delvart A, et al.; 2022)
The drug delivery system prepared under nanotechnology conditions has the characteristics of small size, which is conducive to the adsorption and phagocytosis of drugs by cells, thereby promoting the body's absorption of drugs. In addition, it has a larger specific surface area and can load or couple more functional groups or active centers, so the local concentration of the drug at the target is high, thereby improving the efficacy; in addition, it can adsorb, wrap, and bind active molecules. Dispersed or coupled in the system, therefore, the drug can be effectively protected from enzymatic degradation and immune clearance during transport to the target; it can not only transport hydrophilic molecules, but also hydrophobic molecules that are not suitable for intravenous injection sexual molecules. Constructing drug delivery systems is an extremely important use of polymers. Many polymers have been widely used in drug delivery systems. Degradable polymers that are easy to prepare and modify are often candidate carriers for drug delivery. Nanodrug carriers designed based on these polymer materials have good biocompatibility and can not only improve The drug is stable in the blood and has the functions of targeting, sustained release and controlled release, which can significantly extend the action time of the drug, greatly improve the pharmacodynamics and pharmacokinetic properties of the drug, and reduce the patient's The frequency of taking medication increases compliance, which is beneficial to the treatment of stubborn diseases such as diabetes and coronary heart disease. Although nanocarriers have made great progress, various drug delivery systems have been born in the laboratory, and in vitro experiments and animal experiments have also shown good efficacy, but the exploration of safe, effective and stable drug delivery systems suitable for clinical application is still a matter of pharmacy. challenging puzzles. Natural polymer materials often have the advantages of low toxicity and low cost. Among them, dextran is a common natural polymer material. It is a polymer of monomer α-D-glucose. Its main chain is connected through α-(1→6) glycosidic bonds, and the starting end of the branch chain is α-( 1→4) glycosidic bond or α-(1→3) glycosidic bond is connected to the main chain. Its molecular mass and degree of branching are closely related to its source. Dextran is easy to be chemically modified, and various glycoconjugates can be derived through reactions such as etherification, esterification, amidation and oxidation; in particular, dextran has excellent water solubility, biocompatibility and degradability It can also improve the stability of the drug delivery system and avoid sedimentation in the blood circulation. These advantages provide a material basis for the design and preparation of new delivery systems. Inhibiting the activation of complement is its important biological activity; and polysaccharides are important elements in constructing functional drug delivery systems. Polysaccharides such as dextran, chitosan, hyaluronic acid and heparin sulfate have ligand activity. When the system is controlled by these polysaccharides, after modification, the receptor on the target cell specifically interacts with it to trigger phagocytosis, which is an important application of active targeted drug delivery. For these reasons, polysaccharides have become functional molecules that modify or coat drug delivery systems. Recently reported glucan-based drug delivery systems include not only graft modifications of macromolecules derived from chemical synthesis, but also supramolecular complexes (complexes of host molecules and guest molecules) based on non-covalent bond assembly. Some of them, nanocarriers, make full use of the intracellular microenvironment and external stimulation of cells, have the function of controlled release of drugs, and can play a role in increasing bioavailability and improving drug efficacy.
Dextran-Cyanine 3 can be used as a fluorescent marker to label drug carriers, such as nanoparticles, liposomes, etc. This labeling can track the location, distribution, and dynamic changes of drug carriers in the body in real time. By combining drugs with dextran-Cyanine 3, the release process of drugs can be observed and tracked in real time. This visualization method helps to understand the release mechanism, release rate, and interaction between drugs and carriers in the body. Dextran-Cyanine 3-labeled drug delivery systems can be used to evaluate and optimize the efficiency of drug delivery. By observing the fluorescence signal of dextran-Cyanine 3, the drug delivery path, targeting, and drug accumulation at the target site in the body can be understood, thereby adjusting and optimizing the design of the drug delivery system.
Alternate Names:
Dextran-Cy3
Dextran-Cyanine 3 conjugate
Dextran-fluorescent dye conjugate
References:
1. Delvart A, et al.; Dextrans and dextran derivatives as polyelectrolytes in layer-by-layer processing materials - A review. Carbohydr Polym. 2022, 293:119700.
Dextran-based Nanocarriers for Delivery of Bioactives
Curr Pharm Des.
Authors: Ishak RA, Osman R, Awad GA.
Abstract
Background: Dextran (DX) is a natural polysaccharide produced in the laboratory by fermentation of sucrose under the effect of the enzyme DX sucrase (1,6-α-D-glucan-α- glucosyltransferase). After harvesting and purification DX is subjected to cracking and separation to obtain the desired molecular weight.
Methods: The hydroxyl groups present in DX offer many sites for derivatization allowing the production of functionalized glycoconjugates biocompatible compound. DX and its derivatives are getting increased attention for use in core decoration or as carriers in novel drug delivery systems. This includes, among others, ion-pairing, self-aggregate, protein and drug conjugates. DX carriers and camouflaged particles will be dealt with in this review to give emphasis on the great versatility of this natural biocompatible polysaccharide.
Conclusion: With the continuous development in the area of drug delivery, we believe that the unique properties of this versatile nanocarrier platform will elect it as one of the cornerstones of safe nanodelivery systems.
Multivalent dextran hybrids for efficient cytosolic delivery of biomolecular cargoes
J Pept Sci.
Authors: Becker B, Englert S, Schneider H, Yanakieva D, Hofmann S, Dombrowsky C, Macarrón Palacios A, Bitsch S, Elter A, Meckel T, Kugler B, Schirmacher A, Avrutina O, Diederichsen U, Kolmar H.
Abstract
The development of novel biotherapeutics based on peptides and proteins is often limited to extracellular targets, because these molecules are not able to reach the cytosol. In recent years, several approaches were proposed to overcome this limitation. A plethora of cell-penetrating peptides (CPPs) was developed for cytoplasmic delivery of cell-impermeable cargo molecules. For many CPPs, multimerization or multicopy arrangement on a scaffold resulted in improved delivery but also higher cytotoxicity. Recently, we introduced dextran as multivalent, hydrophilic polysaccharide scaffold for multimerization of cell-targeting cargoes. Here, we investigated covalent conjugation of a CPP to dextran in multiple copies and assessed the ability of resulted molecular hybrid to enter the cytoplasm of mammalian cells without largely compromising cell viability. As a CPP, we used a novel, low-toxic cationic amphiphilic peptide L17E derived from M-lycotoxin. Here, we show that cell-penetrating properties of L17E are retained upon multivalent covalent linkage to dextran. Dextran-L17E efficiently mediated cytoplasmic translocation of an attached functional peptide and a peptide nucleic acid (PNA). Moreover, a synthetic route was established to mask the lysine side chains of L17E with a photolabile protecting group thus opening avenues for light-triggered activation of cellular uptake.
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