A review of therapeutic challenges and achievements of methotrexate delivery systems for treatment of cancer and rheumatoid arthritis

Methotrexate (MTX) is one of the most widely studied and effective therapeutics agents available to treat many solid tumors, hematologic malignancies, and autoimmune diseases such as rheumatoid arthritis; however, the poor pharmacokinetic and narrow safety margin of the drug limits the therapeutic outcomes of conventional drug delivery systems. For an improved delivery of MTX, several pathophysiological features such as angiogenesis, enhanced permeability and retention effects, acidosis, and expression of specific antigens and receptors can be used either as targets or as tools for drug delivery. There are many novel delivery systems developed to improve the pitfalls of MTX therapy ranged from polymeric conjugates such as human serum albumin, liposomes, microspheres, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, polymeric micelles, in situ forming hydrogels, carrier erythrocyte, and nanotechnology-based vehicles such as carbon nanotubes, magnetic nanoparticles, and gold nanoparticles. Some are further modified with targeting ligands for active targeting purposes. Such delivery systems provide prolonged plasma profile, enhanced and specific activity in vitro and in vivo in animal models. Nevertheless, more complementary studies are needed before they can be applied in human. This review deals with the challenges of conventional systems and achievements of each pharmaceutical class of novel drug delivery vehicle.