For Research Use Only. Not for Clinical Use.

Glycosylation and polysialylation are two popular techniques for prolonging the half-life of drugs. In the past many years, most of the methods have achieved limited success, but some formulas have enough hope for clinical trials. However, they all show potential as half-life extenders. Some common excellent methods are as follows:

Dextran Conjugation Based Half-Life Extension Service

Dextran has long been used as a drug carrier to confer greater chemical and biological stability to the dextran drug complex. Dextran and dextran derivatives are chemically conjugated to protein by several different methods including periodate oxidation and by enzymatic approaches. Conjugation of dextran was one of the first alternatives to PEGylation. Like PEGylation, half-life extension by dextran conjugation is driven by the increase in hydrodynamic radius, which decreases the renal clearance of the target compound. Studies of carboxypeptidase-dextran conjugates in tumor-bearing Balc/c mice showed that elimination of dextran is size-dependent, with conjugates containing large dextran moieties exhibiting the longest half-life.

Fig.1 Example of dextran architecture. (van Witteloostuijn, 2016)

HESylation Based Half-Life Extension Service

Hydroxyethyl starch (HES) is a modified natural polymer obtained by controlled hydroxyethylation of the plant polysaccharide amylopectin. The conjugation of HES moieties increases the hydrodynamic volume of the modified molecule, thereby making it less clearance susceptible to renal. HESylation has also been shown to increase protein stability by increasing the melting temperature and the enthalpy aggregation of melting as well as decreasing stress-induced.

Fig.2 Examples of HESylation chemistry. (van Witteloostuijn, 2016)

HEPylation Based Half-Life Extension Service

Heparosans, active polymers of HEPylation are natural polysaccharide and biosynthetic precursors of heparin. It is recognized as 'self' inside our body environment and doesn't have any immunogenicity issue. Therefore, it is considered a good option for a biodegradable protein half-life extension moiety. Heparosans shows a 15 h to 8-day long half-life in the bloodstream depending on MW and route of administration.

HAylation Based Half-Life Extension Service

Hyaluronic acid (HA) is a natural polysaccharide with a linear chain and negative charges. It is regarded as biocompatible, nontoxic, and nonimmunogenic. HA is found in different tissues of the human body. Like other half-life extension agents, conjugation of HA to any peptide can increase the size of the protein decreasing renal clearance. HAylation of insulin provided a conjugate with a prolonged and enhanced glucose-lowering effect after administration to diabetic rats, suggesting that HAylation of insulin increases the half-life and facilitates the formation of a soluble depot.

Fig.3 Chemical structure of the repeating GlcA-GalNAc disaccharide that makes up HA. (van Witteloostuijn, 2016)

Custom Services of Other Polysaccharide Based Approaches

Creative Biolabs has focused on the half-life extension drug development for many years and our team is highly qualified and experienced. We are flexible to provide solutions for half-life extension drug development tailored to our customers' unique needs. If you are interested in our half-life extension services, please feel free to contact us for more information.

Reference

1. van Witteloostuijn, S.B.; et al. Half-life extension of biopharmaceuticals using chemical methods: alternatives to PEGylation. ChemMedChem. 2016, 11(22): 2474-2495.

Related Services:

• Dextran Conjugation Based Half-Life Extension Service
• HESylation Based Half-Life Extension Service
• HEPylation Based Half-Life Extension Service
• HAylation Based Half-Life Extension Service