ABSTRACT
Ethylene oxide and propylene oxide block copolymers (pluronics) are widely known as agents that promote drug penetration across biological barriers. We have studied the interaction of normal and malignant blood cells with pluronics L61 and P85 that have different hydrophobicity. SP2/0 myeloma cells accumulated pluronics while normal cells adsorb most of the polymer on the surface. Interaction of pluronics with cells resulted in drastic changes of membrane microviscosity. Tumor cell membrane microviscosity decreased after pluronics adsorption, in contrast to normal cells, whose membrane microviscosity was enhanced. We suppose that sensitivity of tumor cell membrane microviscosity to the pluronics action correlates with its permeability for molecular substances.
Subject(s)
Erythrocytes/drug effects , Lymphocytes/drug effects , Poloxamer/pharmacology , Surface-Active Agents/pharmacology , Animals , Erythrocyte Membrane/drug effects , Erythrocytes/chemistry , Erythrocytes/pathology , Erythrocytes/ultrastructure , Lymphocytes/chemistry , Lymphocytes/pathology , Lymphocytes/ultrastructure , Membrane Fluidity/drug effects , Mice , Mice, Inbred BALB C , Multiple Myeloma/blood , Poloxamer/metabolism , Surface-Active Agents/metabolism , Tumor Cells, CulturedABSTRACT
A new technique for the creation of compounds with targeted action is described. In such compounds, termed respecrins (receptor-specific, screened toxin), a physiologically active component carries an epitope-containing fragment of the target antigen and is screened or masked by antibody specific to this antigen. Interaction of the respecrin with the target cell results in dissociation of this immunocomplex, and thereby activation of the physiologically active component. The kinetics of dissociation of a respecrin during interaction with a cell were investigated by flow cytometry. Possible applications of the principle are illustrated by investigation on the antigen-dependent activation of the mitogenic activity of staphylococcal enterotoxin A.
Subject(s)
Antigens, Surface/immunology , Enterotoxins/metabolism , Immunotoxins/metabolism , Receptors, Cell Surface/immunology , Allosteric Regulation , Animals , Antigen-Antibody Complex , Biological Transport , Cells, Cultured , Epitopes/immunology , Epitopes/metabolism , Flow Cytometry , Humans , Immunotoxins/immunology , Mice , RabbitsABSTRACT
It has been suggested to use surfactant micelles as microcontainers for increasing the efficiency of neuroleptic targeting from blood flow into the brain. The neuroleptic action of haloperidol, intraperitoneally injected into mice in micellar solution of non-ionic block copolymer surfactant (pluronic P-85) in water, increased several-fold if compared with that observed for haloperidol aqueous solution. Incorporation of brain-specific antibodies into haloperidol-containing micelles resulted in additional drastic increase (more than by 2 orders of magnitude) in the drug effect.
