Studies On The Interaction Between Fluoxetine Hydrochloride And Lipid Monolayers At The Air-water Interface

Fluoxetine hydrochloride(FLX)is an antidepressant of the selective serotonin reuptake inhibitors(SSRIs).It is usually used clinically to treat depression,obsessive-compulsive disorder,bulimia nervosa and other diseases.The FLX molecules contain a phenyl group and a tolyl group,a polar head and a hydrophobic body.Therefore,the FLX molecules are considered to be a positively charged amphiphilic molecules.Neutral phosphatidylcholine(PC)and negatively charged phosphatidylglycerol(PG)are the most common phospholipid head groups that constitute lipid monolayers.The phospholipid head group of PC contains a positively charged N(CH3)3+group and a negatively charged phosphate PO2-group.At the air-water interface,during the interaction between FLX and the lipid monolayers,the NH3+ group in the FLX molecule has an electrostatic interaction with the N(CH3)3+group and the P02-group.The electrostatic interaction plays an important role in many membrane binding phenomena,and the amphiphilic nature of FLX can affect the permeability of the lipid monolayers.Therefore,studying the interaction between FLX and lipid monolayers has become an important scientific issue.In this paper,Langmuir-Blodgett(LB)technique was used to prepare the lipid monolayers with different components at the air-water interface.The interaction between FLX and lipid monolayers with different components at different external conditions,such as the concentrations,surface pressures and pH values,was studied from the point of the view of the biophysical.In this paper,not only the effect of FLX on the adsorption behavior of the lipid monolayers and the interfacial behavior of the binary lipid monolayers,but also on the relaxation and dilational viscoelasticity of the ternary lipid monolayers were studied.The atomic force microscopy(AFM)was used to observe the surface morphology of the lipid monolayers before and after adding FLX into the subphase,and the results were verified.The qualitative and quantitative description of the interaction between FLX and lipid monolayers was given.1.The effect of FLX on the adsorption behavior of DPPC monolayers.The adsorption of FLX with different concentrations on DPPC monolayers was studied at the surface pressure of 10 mN/m and 20 mN/m.The results show that:(1)The adsorption of FLX on DPPC monolayers was related to the interaction between FLX and DPPC molecules.The electrostatic interaction between FLX and DPPC molecules was stronger when the surface pressure was 10 mN/m,so the adsorption of FLX on DPPC monolayers was stronger,and the stability of DPPC monolayers was better.(2)As the concentrations of FLX in the subphase increased,the values of the maximum insertion pressure(MIP)and synergy factor(a)increased,which meant that the electrostatic interaction between FLX and DPPC molecules and the adsorption of FLX molecules on DPPC monolayers increased with the increasing of the concentrations of FLX.2.The effect of FLX on the interfacial behavior of DPPC/DPPG mixed monolayers.The effect of the electrostatic interaction between FLX,DPPC and DPPG molecules on the interfacial behavior of DPPC/DPPG mixed monolayers was studied by thermodynamic method.The results showed that:(1)When FLX was added to the subphase,due to the electrostatic interaction between FLX and lipid molecules,the FLX molecules were adsorbed on the DPPC/DPPG mixed monolayers,which changed the arrangement of the lipid molecules at the interface and improved the compressibility and miscibility of DPPC/DPPG mixed monolayers.(2)The formation of DPPC/DPPG mixed monolayers was a spontaneous process at the air-water interface.When FLX was added to the subphase,the repulsive force between DPPC and DPPG in the mixed monolayers was enhanced under the induction of the FLX molecules.Therefore,the mixed system consumed more energy,resulting in the decrease of the stability and the enhancement of the disorder of the mixed monolayers.3.The effect of FLX on the relaxation of DSPC/POPC/CHOL monolayers at different pH values.Change pH values of the subphase(pH=1,4,7 and 10)and use the method proposed by Ter Minassian-Saraga to study the difference in relaxation of the ternary lipid monolayers before and after adding FLX to the subphase.The effect of FLX on the relaxation of the ternary lipid monolayers was analyzed.The results show that:(1)The interaction of the lipid molecules was attractive and the ternary lipid monolayers were stable in the abasence of FLX in the subphase.After addition of FLX in the subphase,the intermolecular attraction decreased,so the stability of the ternary lipid monolayers decreased and the surface morphology of the ternary lipid monolayers changed.(2)When FLX was added to the subphase,there were some substantial differences in the relaxation of the ternary lipid monolayers,which was related to the pH values.The relaxation consisted of three constant rates dissolution steps at pH=1 and 4,and consisted of two constant rates dissolution steps at pH=7.When pH=10,the relaxation was controlled by dissolution first and then by diffusion.With increasing of pH values,the ternary lipid monolayers with FLX in the subphase gradually reached a stable state.4.The effect of FLX on the viscoelasticity of DPPC/POPC/CHOL monolayers.The effect of different concentrations of FLX on DPPC/POPC/CHOL monolayers at ?=10 mN/m,20 mN/m and 30 mN/m were studied.The results showed that the response of the surface pressures of the monolayers to the sinusoidal oscillation of time was nonlinear due to the influence of the viscosity of the monolayers.This was reflected in the higher harmonic frequency in the frequency domain of the response curves and the non-zero total harmonic distortion(THD)of the response curves.In addition,it was found that the phase angle of the surface pressures response curves lagged ? behind that of the molecular area response curves.After Fourier transform(FFT)of the response curves,it was found that the order of harmonic frequency was affected by surface pressure and FLX concentrations.In this paper,the effect of FLX on the different components of the lipid monolayers at air-water interface was studied.The interaction between FLX and lipid monolayers of the different components was different.The stability,compressibility,miscibility and surface morphology of the lipid monolayers were related to the interaction between FLX and lipid monolayers.To study the interaction mechanism between FLX and lipid monolayers was of great biological significance for further research on the drug delivery across membranes and targeted therapy.