NMR Investigation On The Mechanism Of Micellar Solubilization Of Curcumin By Mixed Surfactants

Due to the amphiphilic properties,the solubility and bioavailability of poorly soluble drugs can be improved by surfactants.Combining the utilizing of characteristic of two surfactants,the lowering the CMCs and the reduced dosage of surfactants,mixed surfactants have great potential for the solubilization of drugs.With the advantages of being able to study the chemical environment and intermolecular interactions of each componants in complex multi-systems at the molecular level,nuclear magnetic resonance(NMR)method has become an important tool to study the solubilization of poorly soluble drugs by surfactants.In this paper,the solubilization mechanism of curcumin by two mixed surfactant systems of SDS/Brij35 and SDS/OG is studied by 1H NMR,2D diffusion ordering spectroscopy(DOSY)and NOESY.First,the solubility of drugs and the significance their solubilization are summarized.Then,common drug solubilization methods are introduced and the micellar solubilization method is highlighted.Furthermore,studies of micellar solubilization of drugs are reviewed.Finally,the application of NMR method including 1H NMR,DOSY and NOESY in micellar solubilization of drugs is introduced.Second,the process and mechanism of the micellar solubilization of curcumin by SDS/Brij35 mixed surfactants at different surfactant mole ratios.Firstly,we found that the molar solubilization amount(MSR)of curcumin decreases linearly with the increase of the SDS mole fraction,suggesting that the solubilization of curcumin is neither promoted nor inhibited by SDS/Brij35 mixed surfactants.Secondly,by analyzing chemical shifts,the different CMC values of SDS and Brij35 are obtained at three molar ratios,and Brij35 has two CMC values,indicating that different micelles form at different stages.Then,it is found that the initial solubilization concentration of curcumin and the CMC value fitted by the Brij35 diffusion coefficient are consistent with the CMC2 value of Brij35.Therefore,we speculate that at the CMC2 of Brij35,curcumin begins to solubilize in micelles,resulting the increase of the micellar volume and decreasing the diffusion coefficient.Furthermore,it can be proved by the NOESY spectra that at high concentrations,the mixed micelles with a multilayer structure is formed for all the three systems,in which the palisade layer of the two surfactants and the hydrophobic chains are staggered.And curcumin is also solubilized in these parts.Finally,the similar micelle structure of the mixed micelles and the single micelles may be the reason why the SDS/Brij35 system neither synergizes nor inhibits the solubilization of curcumin.Third,the process and mechanism of the micellar solubilization of curcumin by SDS/OG mixed surfactants at different surfactant mole ratios.First,unlike Brij35,although OG is also an anionic surfactant,its CMC is higher above Brij35 and its ability to solubilize curcumin is weak.When it is mixed with SDS to solubilize curcumin,although the MSR increases with the increase of αSDS,the SDS/OG system inhibites the solubilization of curcumin.Subsequently,we find that the mixed micelles of SDS and OG form synchronously,while different micelles form at different stages for SDS/Brij35 systems.Besides,the greater the OG ratio,the higher the CMC of the mixed micelles.Finally,it has been found that curcumin is not only solubilized in the hydrophobic core but also solubilized in the paraside layer in the SDS/Brij35 system by NOESY spectroscopy.However,in the SDS/OG system,curcumin is mainly solubilized in the hydrophobic core,which may be one of the reasons for the low solubilization capacity of this system.