Alterations in Phospholipid Bilayers Caused by Oxyethylenated Nonylphenol Surfactants

The interactions of oxyethylenated nonylphenols [ethylene oxide units (EO) averaging between 5 and 30] with phosphatidylcholine liposomes were investigated. Three parameters were regarded as corresponding to the effective surfactant/lipid molar ratios at which the surfactant system (a) resulted in the transient liposome reorganization for the release of 50% of 5(6)-carboxyfluorescein (CF) trapped in the liposomes,R50%CF; (b) saturated the liposomes,RSAT; and (c) led to a complete liposome solubilization,RSOL. From these parameters the surfactant partition coefficientsK50%CF,KSAT, andKSOLwere determined. Permeability alterations were determined as a change in CF released from the interior of vesicles and solubilization as a decrease in the static light scattering of liposome suspensions.RSATandRSOLshowed the lowest values in the critical micellar concentration (CMC) range between 0.040 and 0.087 mMand 0.050 and 0.075 mM,respectively [hydrophilic–lipophilic balance (HLB) number ranging between 13 and 16 and 14 and 15], which corresponded approximately to the nonylphenols with 10–20 and 15 EO units, respectively. However,K50%CF,KSAT, andKSOLdrastically decreased as the number of EO units increased, especially in the EO range between 5 and 15. Thus, the highest surfactant affinity with bilayers (maximumKvalues) and its maximum ability to alter these structures (minimumRvalues) were governed by the CMC surfactants and their HLB numbers and, consequently, by the EO units present in the surfactant structure. The free surfactant concentrations were lower than their CMCs at sublytic level, whereas they remained similar to these values during bilayer saturation and solubilization. The nonylphenols investigated showed higher activity versus liposomes than that reported for Triton X-100, the oxyethylenated nonylphenol with an average of 10 ethylene oxide units showing low toxicity in biological tests.