Abstract: The efficiency of methotrexate use in basic therapy of rheumatoid arthritis is limited because of risk of side effects and fast drug efflux from zone of joints as well. The new stabilized form of methotrexate was elaborated with phospholipid micelles as a carrier. The injective form of the preparation Phosphogliv was used for this purpose. Phosphogliv has recently been developed in the Institute of Biomedical Chemistry (Moscow), as the emulsion of 50 nm phospholipid nanoparticles stabilized by glycyrrhizic acid. The conditions of maximal methotrexate incorporation into the phospholipid nanoparticles were optimised under control of HPLC (60% of total methotrexate was associated with nanoparticles, with remaining drug being in free form in the water phase). Such preparation revealed higher therapeutic efficiency in experimental adjuvant arthritis in rats as compared with free methotrexate. The increase of antirheumatoid activity of the elaborated preparation may also be attributed to the influence of glycyrrhizic acid, possessing both antiinflammatory and immune properties. The possibility of clinical employment of a new methotrexate drug form for rheumatoid arthritis treatment is discussed.
Reference: Zykova M.G., Prozorovskiy V.N., Ipatova O.M., Torkhovskaya T.I., Glazatov V.V., Antirheumatoid activity of methotrexate in phospholipid nanoparticles (phosphogliv), Biomeditsinskaya khimiya, 2007, vol:
1. Couvreur P., Vauthier C. (2006) Pharm. Res., 23, 1417-1450.
2. Yih T.C., Al-Fandi M. (2006) J. Cell Biochem., 97, 1184-1190.
3. Drummond D., Meyer O., Hong K., Kirpotin D., Papahadjopoulos D. (1999) Pharmacol. Rev., 51, 691-743.
4. Dolhain R.I., Talk P.P., Dijkmans B.A., De Kuiper P., Breedveld F.C., Miltenburg A.M. (1998) Br. J. Rheumatol., 37, 502-508.
5. Kukowska-Latallo J.F., Candido K.A., Cao Z., Nigavekar S.S., Majoros I.J., Thomas T.P., Balogh L.P., Khan M.K., Baker J.R.. (2005) Cancer Res., 65, 5317-5324.