PEG & ADC

What is PEG/PEG-linker?

Polyethylene glycol(PEG) is an ethylene glycol polymer with a relative molecular weight of 200 to 8000 or more than 8000. It is composed of repeating oxyethylene groups. It not only has good water solubility but is also soluble in DCM, DMF, benzene, acetonitrile, and ethanol, and other organic solvents.

PEG linker can be used to modify various types of biological drugs. Forming formula materials through positive ion lipophilic liposomal nanoparticles, it will be possible to instantly load targeted molecules and realize the loading of any drug, Which can provide mature technical support for the establishment of a personalized medicine library for cancer patients.

Compared with unmodified drugs, modified drugs often have the following outstanding advantages: 1) stronger biological activity; 2) liposomes have a stronger passive targeting effect on tumors; 3) longer half-life; 4 ) Lower maximum blood concentration; 5) Less fluctuation in blood concentration; 6) Less enzyme degradation; 7) Less immunogenicity and antigenicity; 8) Less toxicity; 9) More Good solubility; 10) Reduce the frequency of medication; 11) Improve patient compliance, improve quality of life, and reduce treatment costs.

Use of PEG

A link between the antibodies and cytotoxic agents plays a key role in the development process, the nature of the linker can significantly affect the potency, selectivity, and pharmacokinetics of the antibody-drug conjugate.

There is hydrophobicity or insoluble with water of many linkers in preparation antibody-drug conjugates. Mostly, the average drug-to-antibody ratio (DAR) or the number of drug molecules per antibody does not exceed 3-4 drug molecules per antibody molecule.

When both the cytotoxic agent and the linker are hydrophobic, tests that attempt to increase DAR often fail. Other unsuccessful reasons may be due to aggregation of antibody-drug conjugates, loss of affinity for the target antigen, or rapid clearance from the circulation.

Hydrophilic linking groups containing sulfonate or PEG can overcome many of the problems encountered by hydrophobic linking groups. The characterized hydrophilic linking groups have high solubility (organic solutions or aqueous solutions).

Compared with the earlier used hydrophobic SPDB and SMCC linkers, branched or multi-arm PEG linkers can bind hydrophobic organic molecular drugs (such as maytansinoids) with a higher DAR ratio, and no causing aggregation or lose the affinity of the resulting conjugate. On the contrary, these results will enable a higher concentration of cytotoxic drug to be delivered to the target cell in that each antibody binding event.

PEG can also use as a potentiator to enhance detection of antigens and antibodies; Increase plasma concentration and increase the area under the plasma concentration-time curve (AUC); Significantly improve the pharmacokinetic properties in vivo; Production the process can achieve high output.

Hydrophilic poly (ethylene glycol) or PEG linkers can be tailored to Non-cleavable, Cleavable, Branched (the effective load of each binding site increases and its 1 connector contains up to 6 toxins), Dissolve hydrophobic cytotoxins.

Conclusion

Since polyethylene glycol has the advantages of hydrophilicity and biological identity, and its advantages can be sublimated by bonding with other substances, it is a favorable decision to adopt the polyethylene glycol route to design a new drug delivery system. With the development and cross-application of chemistry, materials science, medicine, pharmacy and biology, and other disciplines, polyethylene glycol will be more and more widely used in new pharm.

References

[1]https://www.adcreview.com/stable-linker-technologies/peg-linkers