[Liposomal formulation of a methotrexate diglyceride conjugate: activity in methotrexate-resistant leukemia cultured cells].
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 0.075 +/- 0.005 and 16.4 +/- 4.9 microM, respectively, while, in the case of liposomes loaded with MTX-DG, the IC50 values were much closer: 0.77 +/- 0.06 and 3.8 +/- 1.9 microM.
Vodovozova
E L
EL
Kuznetsova
N R
NR
Gaenko
G P
GP
Molotkovskiĭ
Iu G
IuG
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004075:Diglycerides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000473:pathology; D008081:Liposomes; D008727:Methotrexate / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size
D000964:Antimetabolites, Antineoplastic; D004075:Diglycerides; D004337:Drug Carriers; D008081:Liposomes; D008727:Methotrexate