hydroxyethyl starch + methotrexate

Hydroxyethyl starch + methotrexate (HES-MTX) is a polymer-drug conjugate designed to improve the therapeutic profile of the antimetabolite methotrexate. In this system, methotrexate is covalently attached to hydroxyethyl starch (HES), a semi-synthetic polysaccharide, via an ester bond often utilizing a glutamic acid linker. This conjugation increases the molecular weight of the drug, leading to prolonged systemic circulation and preferential accumulation in tumor tissues through the enhanced permeability and retention (EPR) effect. Once at the target site, the active methotrexate is released to inhibit dihydrofolate reductase (DHFR), an enzyme essential for the synthesis of tetrahydrofolate. This inhibition halts the production of thymidylate and purine nucleotides, thereby suppressing DNA synthesis and cell division. HES-MTX has been investigated in preclinical models for the treatment of various cancers, including leukemias and melanoma, demonstrating potential for reduced systemic toxicity compared to free methotrexate.

Other names

methotrexate-hydroxyethyl starch conjugatenanoconjugated methotrexate