Antirheumatic Activity of Methotrexate in Phospholipid Nanoparticles (Phosphogliv)

摘要

The efficiency of methotrexate use in the basic therapy of rheumatoid arthritis is limited because ofrisk of side effects and fast drug efflux from zone of joints as well. We have developed a new stabilized form ofmethotrexate using phospholipid micelles of the injection form of the Phosphogliv preparation as a carrier.Phosphogliv has recently been developed in the Institute of Biomedical Chemistry (Moscow), as the emulsionof 50 nm phospholipid nanoparticles stabilized by glycyrrhizic acid. The conditions of maximal methotrexateincorporation into the phospholipid nanoparticles were optimized under control of HPLC (60% of total meth-otrexate was associated with nanoparticles). Methotrexate in phospholipid nanoparticles exhibited higher ther-apeutic efficiency in experimental adjuvant arthritis in rats than with free methotrexate. (This was evaluated bythe decrease of edema and swelling of joints and inhibition of secondary inflammatory reaction.) The increaseof antirheumatic activity of the developed preparation may also be attributed to the influence of glycyrrhizicacid, possessing both anti-inflammatory and immune properties. It is suggested to use a new form of methotr-exate for intra-articular administration for rheumatoid arthritis treatment.