Effect of CRL-1343 and HSA-157, non-ionic detergents on the bilayer and hexagonal phase transition temperature

Abstract

In recently developed non-ionic surfactants called CRL-1343 and HSA-157 (Polyoxyethylene esters of C18 fatty acid, the second compound differs from the first, in having an ester linkage instead of ether link. The second compound, has a hydroxy fatty acid rather than a plain fatty acid component) with low toxicity in vivo, and an ability to reverse the multidrug resistance in human epidermoid carcinoma cells in vitro. The compounds were shown to affect the bilayer and hexagonal phase transition in liposomes. The bilayer phase transition temperature of liposomes composed of dipalmitoylphosphatidylcholine, and encapsulated self quenched doxorubicin, was found to be 40°C, as measured by fluorescence assay. The phase transition measured by this method was found to be in good agreement with the phase transition measured by other techniques such as differential scanning calorimeter (DSC). Addition of the non-ionic detergent HSA-157 to these liposomes, at a concentration of 400 nmol, lowered the transition temperature to 30°C, while adding CRL-1343 to the same control liposomes at concentration of 10 nmol lowered the transition temperature to 28°C. The hexagonal phase transition temperature of N-(7-nitro-2,1,3-benzoxadiazol-4yl) phophatidylethanolamine (NBD-PE) labeled egg PE, was found to be 40°C as determined by fluorescence spectroscopy, and which is in good agreement with DSC measurements. Addition of HSA-157 to the liposomes at the same concentration used before, increased the phase transition temperature to 45°C, while adding CRL-1343 to the same control liposomes at the same concentration used before, increase the hexagonal transition temperature to 50°C. Our results provide an improved knowledge to understand the mechanism of the newly developed non-ionic surfactant in reversing the MDR, and suggest that those surfactants affect the permeability of membranes, by changing their phase transition behavior.