Theoretical And Experimental Studies On The Interaction Of Curcumin Drugs With Different Surfactants

Curcuma,a tropical plant,is a member of the ginger family.Increasing attention has been paid to curcuminoids due to their low intrinsic toxicity and a number of potentially beneficial biological effects.However,curcuminoids are poorly soluble in water at acidic p H and are easily degraded in neutral and alkaline aqueous solutions.Therefore,oral curcuminoids are not well absorbed by the human body.Surfactant micelles with amphiphilic properties show great biocompatibility as drug delivery systems.The encapsulation of drugs by micelles can improve the aqueous solubility and stability.Based on extensive literature survey and the actual situation in our laboratory,we investigated the interaction between curcumin and different surfactants using molecular dynamics simulation combined with a variety of spectroscopy methods in this paper.It was divided into the following four parts:Part I:Molecular dynamics simulation was used to study the interaction between curcumin and dodecyltrimethylammonium bromide（DTAB）in the chapter.Three states of DTAB monomer,premicelle and micelle were constructed by changing the number of added DTAB molecules to explore the interaction mode of curcumin with DTAB in different aggregation states.Distance distribution,number density distribution,electrostatic potential distribution and energy decomposition were used to clarify the bonding structure and mechanism of interaction.The simulation results were compared with literature values.DTAB of monomer and premicelle states interacted with curcumin through electrostatic and hydrophobic interactions,respectively.When the surfactant concentration was above the critical micelle concentration（cmc）,curcumin was solubilized into the micelle and located at the palisade layer.Part II:The interaction between bisdemethoxycurcumin（BDMC）and nonionic surfactants（Tween 20 and Tween 60）was investigated in this chapter.The thermodynamic parameters of the interaction between BDMC and Tween 20/Tween 60 micelles were obtained by spectroscopy techniques.The negative value ofΔG,ΔH andΔS indicated that the binding of BDMC with Tween 20 and Tween 60 micelles was spontaneous and the main driving forces were hydrogen bonding and van der Waals forces.The results of Cu²⁺-induced fluorescence quenching,fluorescence polarization experiments,time-resolved fluorescence and NMR spectroscopy implied that BDMC may exist in the hydrophilic PEO layer of Tween micelles.The results of coarse-grained molecular dynamics simulation confirmed the reliability of the experimental results from a microscopic point of view.Finally,the phase solubility method was used to verify the solubilization effect of Tween micelles on BDMC.Part III:The interaction of BDMC with cetyltrimethylammonium bromide（CTAB）and Tween 20/Tween 60 mixed surfactants was investigated in this chapter.First,taking the enhanced stability and solubility of BDMC as the goal,the optimal ratio of CTAB to Tween 20/Tween 60 of the mixed surfactant was obtained through response surface design,which was 5:1.The solubilization effect of mixed surfactants on BDMC was obtained through solubility experiments.Stability experiments proved that mixed surfactants can improve the stability of BDMC.The effect of mixed surfactants on the stability of BDMC was explored.The thermodynamic parameters of the interaction between BDMC and CTAB+Tween 20/Tween 60 mixed micelles were obtained through spectroscopy experiments.The negative values ofΔG and positive values ofΔH andΔS indicated that the binding of BDMC with mixed micelles was spontaneous and the main driving forces were hydrophobic force forces.The results of Cu²⁺-induced fluorescence quenching,fluorescence polarization experiments,time-resolved fluorescence and NMR spectroscopy implied that BDMC may exist in the hydrophobic alkyl chain of mixed micelles.Part IV:The interaction of BDMC with sodium lauryl sarcosinate（SDDS）and Tween20/Tween 60 mixed surfactants was investigated in this chapter.First,taking the improve of solubility of BDMC as the goal,the optimal ratio of SDDS to Tween 20/Tween 60 of the mixed surfactant was obtained through response surface design,which was 1:5.The solubilization effect of mixed surfactants on BDMC was obtained through solubility experiments.The thermodynamic parameters of the interaction between BDMC and SDDS+Tween 20/Tween 60 mixed micelles were obtained from spectroscopic experiments.Cu²⁺induced fluorescence quenching experiment,fluorescence polarization experiment,time-resolved fluorescence experiments and NMR spectroscopy experiment were used to obtain the position of BDMC in the mixed micelle.The negative value ofΔG and positive values ofΔH andΔS indicated that the binding of BDMC with mixed micelles was spontaneous and the main driving forces were hydrophobic force forces.The results of Cu²⁺-induced fluorescence quenching,fluorescence polarization experiments,time-resolved fluorescence and NMR spectroscopy implied that BDMC may exist in the hydrophobic alkyl chain of mixed micelles.The different effects of SDDS+Tween and CTAB+Tween mixed micelles on BDMC are discussed.