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  • Title: Increased accumulation of drugs in multidrug-resistant cells induced by liposomes.
    Author: Warren L, Jardillier JC, Malarska A, Akeli MG.
    Journal: Cancer Res; 1992 Jun 01; 52(11):3241-5. PubMed ID: 1591733.
    Abstract:
    A multidrug-resistant cell such as the human lymphoblastic leukemic cell CEM/VLB100 accumulates far less vinblastine (VLB) than its drug-sensitive parent, CEM. When CEM/VLB100 cells are exposed to liposomes consisting of the phospholipids cardiolipin, dioleoylphosphatidic acid, or phosphatidylinositol bearing unsaturated fatty acids and then tested for uptake of VLB, accumulation of drug rapidly rises to levels approaching those of CEM cells, which are relatively unaffected by the liposome treatment. The liposomes are not carriers of entrapped drug. Phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine are inactive, and the addition of cholesterol to liposomes inhibits uptake. Exposure of cells to liposomes does not appear to alter the efflux of drugs. We suggest that the liposomal lipids, introduced into the plasma membranes of CEM/VLB100 cells, change their properties so that accumulation of drugs by cells is largely restored. The cytotoxicity of VLB in CEM/VLB100 cells is increased approximately 10-fold by cardiolipin liposomes.
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