For Research Use Only. Not for Clinical Use.

Overview of Dextran Conjugation

Dextran is a branched natural polysaccharide containing α-1,6-linkage between glucose as the backbone with α-1,3 linked branches. It is a biocompatible, biodegradable proved material. Dextran is water-soluble and is easy to modify with other functional groups to achieve environment-responsive properties. Due to its hydrophilicity, dextran itself may also be conjugated to other drugs for enhancing circulation time. The highly versatile nature of the dextran conjugates can overcome many practical difficulties in delivering chemotherapeutics, genes, and other drugs due to the surface nature including biocompatibility, degradability, and size/dimension are adjustable.

Fig.1 Conjugation of dextran with budesonide or dexamethasone. (Varshosaz, 2012)

Some Popular Synthesis Methods of Dextran Conjugates

• Direct Esterification
  Many ester prodrugs of dextran have been developed by its conjugation with acidic drugs to prolong drug release. This type of linkage is formed by conjugation of hydroxyl groups of dextran in the presence of N, N'-dicyclohexylcarbodiimide with carboxylic acid drugs. Another type of dextran ester is dextran ester-olefin compound copolymer.
• Carbonyldiimidazole Activation Method
  Activation of dextran hydroxy groups may be done with carbonyldiimidazole then amino groups are introduced by attaching ethylenediamine and reacting amino groups with a succinimidyl-activated derivative of other hydroxyl-containing substances like PEG.
• Carbonate or Carbamate Ester Method
  Drugs containing a hydroxyl or amine group can be coupled to dextran in the form of carbonate or carbamate ester linkage, respectively.
• Periodate Oxidation Method
  Enzymes and proteins are attached to dextrans and other polysaccharides by periodate oxidation of dextran which produces dialdehyde dextran.
• Cyanogens Bromide Activation Method
  Amine-containing drugs and proteins may be attached to dextran or other polysaccharides by the cyanogens bromide activation of dextran.
• Etherification of Dextran
  Ethers of dextran are made by irreversible nucleophilic substitution using aliphatic or aromatic halides, sulfates, or epoxides, whereas reversible etherification is achieved via Michael addition of α, β-unsaturated reagents such as acrylonitrile, acrylamide, and methyl vinyl sulfone.

  
  

Example of Increased Circulatory Half-Life of Liposomes After Conjunction with Dextran

In this study, scientists have investigated the effect of dextran conjugation to small unilamellar liposomes on the rate of clearance of their entrapped solute contents from the blood and the uptake by different tissues of the injected animals. The results show that such dextran conjugated liposomes can serve the dual purpose of extending the duration of drugs in circulation considerably and of protecting the drug from the hostile environment. Regardless of the mechanism by which dextran promotes the stability of liposomes in vivo, dextran conjugated liposomes should provide an effective means for controlled drug release over longer periods. Such controlled release may be of particular importance in diseases where the slow release of a drug is essential.

Fig.2 Clearance of different types of liposomes from the circulation of mice. (▲), Liposome-PE (control); (●), Liposome-PE (10 mol%)-dextran; (○), liposome-PE (18 mol%)-dextran; (Δ), liposome-PE (30 mol%)-dextran. (Pain, 1984)

Custom Services of Dextran Conjugation Based Half-Life Extension

Dextran conjugation via a spacer has been extensively explored for small molecules but has also been applied to peptides and enzymes. Creative Biolabs has focused on the half-life extension drug development for many years. We have a very professional technical team and rich project experience in dextran conjugation-based half-life extension drug development. If you have any problems with half-life extension drug development or you are interested in our services, please do not hesitate to contact us for more details.

References

1. Varshosaz. J. Dextran conjugates in drug delivery. Expert opinion on drug delivery. 2012, 9(5): 509-523.
2. Pain, D.; et al. Increased circulatory half-life of liposomes after conjunction with dextran. Journal of Biosciences. 1984, 6(6): 811-816.