Dextran is a nature polysaccharide that contains glucose molecules bound by -(16) glycosidic bonding. With the use of water-soluble, functionalization, and biodegradability dextran is used extensively for various applications, including as a drug delivery agent. But as a way to perform more effectively in this role it can be modified in ways of optimizing its efficiency and functionality. A modification is that aldehyde groups are added into the dextran system, so Dextran-Aldehyde. This aldehyde-functionalized derivative has unique features which are applicable in drug delivery systems in areas that require specific release, controlled release, and biocompatibility. Aldehyde groups placed on the dextran polymer facilitate covalent bonds with all kinds of biomolecules. The aldehyde functional group on Dextran-Aldehyde is a highly configurable reactive site for further modification making it a perfect candidate in drug delivery systems. The addition of aldehyde groups allows for a chemical retransformation that gives dextran to increase reactivity so that it is covalently attached to amine groups in proteins, peptides, drugs or bioactive molecules. It has more reactivity so that stable conjugates with various therapeutic agents will help the drugs in the sense that solubility, stability, and bioavailability. Also, these aldehyde groups can crosslink dextran molecules and generate nanoparticles, hydrogels, or microparticles to encapsulate drug and release controlled. This ability can be used especially when the long and sustained release of drugs are required such as in the care of chronic disease or locally targeted therapy. Because Dextran-Aldehyde is able to form diverse structures and conjugates with multiple therapeutic molecules makes it a highly flexible and highly scalable material in modern drug delivery systems. One of the best benefits of Dextran-Aldehyde in the drug delivery is that its aldehyde is able to target particular area. The aldehyde-linked parts of dextran polymer facilitate conjugation with targeted ligands, antibodies, peptides, or aptamers that precisely recognize and bind to receptors on the surface of disease cells, such as cancer cells or infected cells. This type of targeted delivery makes sure that the drug gets directly to the site of action, reducing a healthy tissues' exposure to the drug and reduced side effects. The hydrophilic nature of dextran helps make conjugates retain solubility and stability in aqueous environment that makes drug delivery possible. This feature makes Dextran-Aldehyde an attractive drug design that must have specific target groups (e.g., cancer therapy, gene delivery, or tissue engineering). Changing the polymer and the release drug are also great as it enhances the therapeutic effect of the delivery process. Due to the unique chemical properties of Dextran-Aldehyde, drug delivery devices, from injectable hydrogels to nanoparticle devices, have already found use. One of the most relevant applications is that of nanoparticle drug delivery systems that would contain drugs at the base or the surface by functionalizing dextran with aldehyde groups. Functionalizing dextran and aldehyde groups is what will allow the nanoparticles to hold drugs in the centre of their core or on top. When the dextrans and aldehyde groups work together to create nanoparticles that capture drugs in their core or on their surface, this nanoparticle is also designed to release contents based on environmental variables such as pH fluctuations, temperature fluctuations, or enzyme activation. The aldehyde groups can enable dextran the creation of nanoparticles as well as the conjugation of targeted molecules to assure that the drug is given only to the intended target. In cancer therapy, for example, the function of Dextran-Aldehyde nanoparticles can be functioned with ligands binding to cancer cell receptors, so that chemotherapeutic drugs are directly delivered to the tissues of a tumor and reduced systemic toxicity. How Dextran-Aldehyde is used to deliver drugs mainly depend on how the aldehyde group covalently bonds to other molecules and when the group does crosslinks to create the desired structures. Reactivity of aldehyde group can be converted into conjugating other biomolecules, including antibodies, peptides or even small molecules and creating more complicated drug delivery methods. For instance, some uses the aldehyde group for the Schiff base links with amine-contained compounds are possible, with additional modifications to assure stability and controlled drug release.
Figure 1. Synthesis of dextran aldehyde, and base-catalysed hydrolysis of the inter-chain hemi-acetal cross-linkages. (Cabral JD, et al.; 2014)
Not only can the Dextran-Aldehyde's crosslinking ability produce stable conjugates, but its hydrogel-based system which encapsulates and slowly releases drugs over a longer period of time, makes Dextran-Aldehyde useful in applications where sustained drug release is required, like in the release of anticancer drugs, vaccines, or proteins. That makes Dextran-Aldehyde especially effective for applications where continuous drug release is needed such as in delivering anticancer agents, vaccines, proteins. Dextran-Aldehyde is also possible for tissue engineering scaffolds and regenerative medicine. The aldehyde groups can help the binding of growth factors or stem cells to the dextran backbone and create scaffolds that deliver therapeutic products and allow tissue regeneration, and these scaffolds can also be designed to facilitate certain cellular behaviors, such as differentiation or proliferation, which are important to the regenerative therapies. These scaffolds can also be programmed to enable specific cellular mechanisms, including differentiation or proliferation, which are very important for regenerative medicine. The versatile properties of Dextran-Aldehyde in manufacturing many different types of structures (microparticles, hydrogels, nanoparticles) add further makes it valuable for these types of use.
Biocompatibility and biodegradability is arguably one of the most crucial advantages in the delivery of drugs. Dextran, a natural polysaccharide that originates from glucose is a high biocompatibility substance, and it does not induce adverse immune reactions if you re-introduce into your body. This mean that it does not accumulate in your body with any toxic product. Dextran is degraded into non-toxic product in time which minimizes the risk of overcrowding in the body. This also applies to long term treatment therapies which involve a high dose of the drug release long-term. Dextran's biodegradability assures that the polymeric carrier that will be not able to be left after the therapeutic effect achieved. Biocompatibility and biodegradability also makes Dextran-Aldehyde one of the more attractive options for the use of systemic and local drug delivery from cancer treatment to tissue engineering. Another benefit of Dextran-Aldehyde is the covalent bonding with all sorts of biomolecules such as small molecule drugs, proteins and nucleic acids, therefore a very adaptability in the development of drug delivery systems that meet specific therapeutic needs. Due to the capability of Dextran-Aldehyde, the ability to build stable conjugates makes it very valuable for improving the solubility, stability, and bioavailability of drugs that are less soluble. Furthermore, by including aldehyde groups, we can create drug-loaded nanoparticles or hydrogels that release controlled doses for extended periods which will lower the amount of repeated dosing required and improve patient compliance. To deliver targeted drugs, the aldehyde groups are made it easy to conjugate the targeted ligands. In response to the drug being sent exactly to the site of action (like a tumor or inflammation), minimising side effects, while improving therapeutic success. Among them is the stability of Schiff base bonds that are formed between aldehyde molecules and amine-rich drugs or biomolecules, which can undergo hydrolysis or enzymatic cleavage, leading to early drug release or less stability in the formulation. Fortunately, scientists are looking at how to make the resulting conjugates more stable by using more stable crosslinking chemistry or designing modified dextrans with better stability profiles. Also, although Dextran-Aldehyde is biocompatible and biodegradable, the rate of biodegradation can vary depending on formulations, which may impact drug release profile. The improvement of the degradation rate according to the therapeutic needs is another area in which research is carried out on Dextran-Aldehyde-based drug delivery systems.
Alternate Names:
Aldehyde-Modified Dextran
Dextran Aldehyde Derivative
Dextran-CHO
Dextran with Aldehyde Groups
Aldehyde-Functionalized Dextran
Dextran-Alkyl Aldehyde
Dextran Aldehyde Conjugate
References:
1. Cabral JD, et al.; Synthesis, physiochemical characterization, and biocompatibility of a chitosan/dextran-based hydrogel for postsurgical adhesion prevention. J Mater Sci Mater Med. 2014, 25(12):2743-56.
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