Letter to the Editor

Liposomal Formulation of a Methotrexate Diglyceride Conjugate: Activity Toward a Culture of Methotrexate-Resistant Leukemia Cells

E.L.Vodovozova1#, N.R.Kuznetsova1, G.P.Gaenko1 and Jul.G.Molotkovsky1

#Phone: (495) 330-6610; fax: (495) 330-6601; e-mail: elvod@ibch.ru

1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia

Received: December 11,2006: in final form: December 19,2006

Abstract.We have recently synthesized a lipid conjugate of the anticancer agent methotrexate (MTX-DG) and showed that the conjugate is quantitatively included in the lipid bilayer of liposomes prepared by a standard extrusion technique from an 8:1:1 (mol) egg phosphatidylcholine-yeast phosphatidylinositol-MTX-DG mixture. Both the size of liposomes (126 30 nm) and the MTX-DG concentration (4.4 mM) are relevant for systemic injections in mammals. The liposomal formulation of MTX-DG was shown to overcome the resistance of tumor cells in vitro to methotrexate: the cytotoxic activities (IC50) of MTX in cultures of the human T-lymphoblastic leukemia cell line CEM-CCRF and the MTX-resistant subline CEM/MTX were 0.0750.005 and 16.44.9 μM, respectively, while, in the case of liposomes loaded with MTX-DG, the IC50 values were much closer: 0.770.06 and 3.81.9 μM.

Key words:drug resistance of cells,lipophilic prodrug,liposomes,methotrexate

Russian Journal of Bioorganic Chemistry 2007, 33 (4): 436-438