PotM: Functionalized Dextrans

The design and synthesis of drug delivery systems suitable to address clinical demands is a major topic of ongoing research efforts. Examples include synthetic as well as natural materials. Compared to “unnatural” polymers, which might accumulate in the body, natural ones such as proteins or polysaccharides benefit of biocompatibility, non-toxicity, biodegradability, and non-immunogenicity which reduces the likelihood of side effects. In this context, dextran-based delivery systems have been studied extensively in the past years.

Dextran was first discovered by Louis Pasteur as a microbial product in wine. The polymer consists of the monomer alpha-D-glucose, mainly linked by alpha-1,6-glycosidic bonds with branches of alpha‑1,2, alpha-1,3, and alpha-1,4 linkages.

Dextran main chain (alpha-1,6-linked glucose moieties) with alpha-1,3-linked side chain.

Besides the above-mentioned advantages of a natural polymer, Dextran can easily be chemically modified and shows excellent solubility in a variety of solvents such as water, DMSO, ethylene glycol, and glycerol. Unlike other polysaccharides, dextran is barely attacked by common amylases and is stable against chemical and enzymatic degradation during transport through the stomach and small intestine. Also, the neutral charge of dextran is another feature that facilitates the delivery efficacy.

Applications for dextran-based materials include imaging, flow cytometry, cancer therapy, pinocytosis, immune-histochemistry, T-cell detection and multiplex assays.

To conjugate or modify dextrans, we offer mono-end-functionalized derivatives (e.g. amine, thiol, biotin) with molecular weights ranging from 10 to 500 kDa. Further derivatives are available on request.

The application panel of dextrans ranges from all types of conjugation for drug and vaccine delivery up to surface modification for diagnostics.

→ For more information about drug delivery technologies, download our brochures about PEGylation and Polymer Therapeutics! 

References:

Simultaneous determination of intraluminal lysosomal calcium and pH by dextran-conjugated fluorescent dyes; P. Pihán, P. Nunes-Hasler, N. Demaurex, C. Hetz; Methods in cell biology 2021; 165: 199-208.

Recent advances in dextran-based drug delivery systems: From fabrication strategies to applications; Q. Hu, Y. Lu, Y. Luo; Carbohydr Polym 2021; 264: 117999. https://doi.org/10.1016/j.carbpol.2021.117999

Dextran-Functionalized Quantum Dot Immunoconjugates for Cellular Imaging; K. Rees, M. Massey, M. V. Tran, W. R. Algar; Methods Mol Biol 2020; 2135: 143-168. https://doi.org/10.1007/978-1-0716-0463-2_8

Cytosolic Uptake of Large Monofunctionalized Dextrans; W. Chyan, H. R. Kilgore, R. T. Raines; Bioconjug Chem 2018; 29: 1942-1949. https://doi.org/10.1021/acs.bioconjchem.8b00198

Acetalated Dextran: A Tunable and Acid-Labile Biopolymer with Facile Synthesis and a Range of Applications; E. M. Bachelder, E. N. Pino, K. M. Ainslie; Chem Rev 2017; 117: 1915-1926. https://doi.org/10.1021/acs.chemrev.6b00532

Use of dextran nanoparticle: A paradigm shift in bacterial exopolysaccharide based biomedical applications; A. Banerjee, R. Bandopadhyay; Int J Biol Macromol 2016; 87: 295-301. https://doi.org/10.1016/j.ijbiomac.2016.02.059

The effect of the size of fluorescent dextran on its endocytic pathway; L. Li, T. Wan, M. Wan, B. Liu, R. Cheng, R. Zhang; Cell Biol Int 2015; 39: 531-9. https://doi.org/10.1002/cbin.10424

Dextran as a generally applicable multivalent scaffold for improving immunoglobulin-binding affinities of peptide and peptidomimetic ligands; J. Morimoto, M. Sarkar, S. Kenrick, T. Kodadek; Bioconjugate chemistry 2014; 25: 1479-1491.

Dextran conjugates in drug delivery; J. Varshosaz; Expert Opin Drug Deliv 2012; 9: 509-23. https://doi.org/10.1517/17425247.2012.673580

Dextran—the polysaccharide with versatile uses; A. L. Bhavani, J. Nisha; Int J Pharm Biol Sci 2010; 1: 569-573. 

Versatile and efficient synthesis of protein-polysaccharide conjugate vaccines using aminooxy reagents and oxime chemistry; A. Lees, G. Sen, A. LopezAcosta; Vaccine 2006; 24: 716-29. https://doi.org/10.1016/j.vaccine.2005.08.096

Nanoparticles on the basis of highly functionalized dextrans; T. Liebert, S. Hornig, S. Hesse, T. Heinze; J Am Chem Soc 2005; 127: 10484-5. https://doi.org/10.1021/ja052594h

PEGylated dextran as long-circulating pharmaceutical carrier; A. N. Lukyanov, R. M. Sawant, W. C. Hartner, V. P. Torchilin; Journal of Biomaterials Science, Polymer Edition 2004; 15: 621-630.

Pathway tracing using biotinylated dextran amines; A. Reiner, C. L. Veenman, L. Medina, Y. Jiao, N. Del Mar, M. G. Honig; J Neurosci Methods 2000; 103: 23-37. https://doi.org/10.1016/s0165-0270(00)00293-4

Activation of soluble polysaccharides with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) for use in protein-polysaccharide conjugate vaccines and immunological reagents. II. Selective crosslinking of proteins to CDAP-activated polysaccharides; D. E. Shafer, B. Toll, R. F. Schuman, B. L. Nelson, J. J. Mond, A. Lees; Vaccine 2000; 18: 1273-81. https://doi.org/10.1016/s0264-410x(99)00370-9

Dextran polymer conjugate two-step visualization system for immunohistochemistry; M. Vyberg; Appl Immunohistochem 1998; 6: 3-10.

Activation of soluble polysaccharides with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate for use in protein-polysaccharide conjugate vaccines and immunological reagents; A. Lees, B. L. Nelson, J. J. Mond; Vaccine 1996; 14: 190-8. https://doi.org/10.1016/0264-410x(95)00195-7

Picogram quantities of anti-Ig antibodies coupled to dextran induce B cell proliferation; M. Brunswick, F. D. Finkelman, P. F. Highet, J. K. Inman, H. M. Dintzis, J. J. Mond; J Immunol 1988; 140: 3364-72. https://doi.org/10.4049/jimmunol.140.10.3364

On the viscous fermentation and the butyrous fermentation; L. Pasteur; Bull. Soc. Chim. Paris 1861; 11: 30-31.

The dextrans as vehicles for gene and drug delivery; S. Huang, G. Huang; Future Medicinal Chemistry 2019; 11(13).  https://doi.org/10.4155/fmc-2018-0586

Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer; A. Grebinyk, S. Prylutska, S. Grebinyk, S. Ponomarenko, P. Virych, V. Chumachenko, N. Kutsevol, Y. Prylutskyy, U. Ritter, M. Frohme; Nanoscale Adv. 2022; 4: 5077-5088. https://doi.org/10.1039/D2NA00353H