Methotrexate transport mechanisms: the basis for targeted drug delivery and ß-folate-receptor-specific treatment

Clin Exp Rheumatol. 2010 Sep-Oct;28(5 Suppl 61):S40-5. Epub 2010 Oct 28.


Methotrexate (MTX) plays a pivotal role in the treatment of rheumatoid arthritis (RA). The transport mechanisms with which MTX reaches is target after application are an important part of MTX pharmacology and its concentration in target tissue such as RA synovial membrane might strongly influence the effectiveness of the drug. Physiological plasma protein binding of MTX to albumin is important for the distribution of MTX in the body and relative high concentrations of the drug are found in the liver. However, targeted drug delivery into inflamed joints and increased anti-arthritic efficiency can be obtained by covalent coupling of MTX ex-vivo to human serum albumin (MTX-HSA) or in-vivo to endogenous albumin mediated through the MTX-pro-drug AWO54. High expression of the folate receptor β (FR-β) on synovial macrophages of RA patients and its capacity to mediate binding and uptake of MTX has been demonstrated. To further improve drug treatment of RA, FR-β specific drugs have been developed and were characterised for their therapeutic potency in synovial inflammation. Therefore, different approaches to improve folate inhibitory and FR-β specific therapy of RA beyond MTX are in development and will be described.

Publication types

  • Review

MeSH terms

  • Animals
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / pharmacokinetics*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Biological Transport
  • Drug Carriers*
  • Folate Receptor 2 / metabolism*
  • Humans
  • Macrophages / metabolism
  • Methotrexate / administration & dosage
  • Methotrexate / blood
  • Methotrexate / pharmacokinetics*
  • Protein Binding
  • Serum Albumin / metabolism*
  • Synovial Membrane / metabolism*
  • Tissue Distribution


  • Antirheumatic Agents
  • Drug Carriers
  • Folate Receptor 2
  • Serum Albumin
  • Methotrexate