The Interaction Between Surfactant Vesicles And Amphiphilic Molecules With Steroid Structure

Surfactant aggregates are unique biomimetic drug carrier,as they have functions with drug delivery and slow release.Thus regulating the composition,stability,and microstructure of the aggregates is of importance.In this thesis,we constructed amphiphilic molecular aggregates?micelles,vesicles?by mixed surfactants.The aggregation behavior and thermodynamics of intermolecular interactions between amphiphilic molecular aggregates and sodium deoxycholate?Na DCA?,sodium cholate?Na CA?or dextran modified with bile acid salt were studied by thermodynamic methods?isothermal titration calorimetry?ITC?and differential scanning calorimetry?DSC?,combined with fluorescence measurements,turbidity measurements and Cryo-Transmission electron microscopy?Cryo-TEM?.The effects of hydrophobic side chain,cationic head groups?chemistry and charge?,composition of solution and surfactant concentration were analyzed in detail on the molecular self-assembling process in these complex fluids,and the synergistic effect between amphiphilic molecules was discussed.Furthermore,for the mixed systems with cationic gemini surfactant(C₁₂C_SC₁₂Br₂,S=3,10),the effect of the spacer length on the aggregation processes of oppositely charged mixed surfactant vesicles was also analyzed.On the basis of understanding their thermodynamic properties on these complex fluids,the effects of the side group bile salt and dextan backbone of the polymer on the morphologies and phase transition of the mixed vesicles also were carefully studied in terms of macroscopic thermodynamics.The research content and results are summarized as follows:1.The two kinds of the oppositely charged amphiphiles-C₁₂C_SC₁₂Br₂/Na DCA and C₁₂C₆C₁₂Br₂/Dex-15CACOONaFor C₁₂C_SC₁₂Br₂?S=2,6,10?/Na DCA system,the critical micelle concentration(cmc_mix)was obtained by Steady-state fluorescence probe method;the critical concentrations?C_P,C_R,C_M?and the enthalpy changes for various phase transitions in the process of interaction between C₁₂C₆C₁₂Br₂ and Na DCA were charecterized by ITC.In comparison with C₁₂C_SC₁₂Br₂/Na CA system,C₁₂C_SC₁₂Br₂/Na DCA mixture has a wider concentration range in LC phase region due to the different structures of Na CA and Na DCA.For the mixed system of oppositely charged C₁₂C₆C₁₂Br₂/Dex-15CACOONa,from the curves of observed enthalpy(?H_obs)or turbidity?OD?as a function of the gemini concentration(C_gemini)a variety of the critical concentrations and the corresponding transition enthalpies were obtained,and aggregate size and phase were observed by Cryo-TEM.The gemini surfactant can crosslink together the pendant aggregates from different polymers by electrostatic forces and hydrophobic associations,and thus it can be considered as a high efficient crosslinker with double heads and chains.The cross-linking happens far from their charge neutralization,resulting in the negative charge-rich aggregates.By analyzing the effects of the various factors,such as the surfactant structure,the conformations of the polyelectrolyte and the properties of the grafted groups,on the interaction between C₁₂C₆C₁₂Br₂ and Dex-15CACOONa,the driving force of aggregate formation and the thermodynamic mechanism of intermolecular interaction were proposed.2.The mixtures of Na DCA/DDAB/SDS and Dex-3DCA/DDAB/SDSThe mixed DDAB/SDS(x _SDS=0.6)vesicles were prepared.The interaction enthalpies(?H_obs)of Na DCA with DDAB/SDS mixed vesicles were determined by ITC.The polydispersity of DDAB/SDS mixed vesicles was characterized by Cryo-TEM.The morphology and size of the DDAB/SDS mixed vesicles are dependent on the molar fraction of Na DCA.The phase transition temperature?T_m?of the gel to liquid crystal of Na DCA/DDAB/SDS mixed vesicles was measured by differential scanning calorimetry?DSC?.It was found that the addition of Na DCA reduced the T_m of DDAB/SDS mixed vesicles,indicating that Na DCA weakened the stability of vesicles.For the mixed system?Dex-3DCA/DDAB/SDS?,the regulation of Dex-3DCA on DDAB/SDS mixed vesicles is different from the case containing free Na DCA due to the restriction of the dextran backbone.The polymer side chains?-DCA?may be inserted into the bilayer of the DDAB/SDS mixed vesicle and the polymer chains are wrapped around the outer surface of the vesicles,resulting in changing the size and shape of the vesicles,and increasing the phase transition temperature?T_m?,as a result Dex-3DCA just did improve the stability of DDAB/SDS mixed vesicles.3.The mixed systems of Na DCA/C₁₂C_SC₁₂Br₂/SDS and Dex-3DCA/C₁₂C_SC₁₂Br₂/SDSTwo systems(C₁₂C₃C₁₂Br₂/SDS and C₁₂C₁₀C₁₂Br₂/SDS)were chosen to prepare vesicles to study the effects of spacer of gemini on the morphology of mixed vesicles.The C₁₂C₃C₁₂Br₂/SDS mixture can form small spherical vesicles,whereas C₁₂C₁₀C₁₂Br₂/SDS can form large multi-layer and multi-core vesicles,as the gemini surfactant has a long alkyl chain as the spacer group.NaDCA can regulate the aggregates of C₁₂C₃C₁₂Br₂/SDS from spherical vesicles to ellipsoid vesicles,but deoxycholic acid modified polymers?Dex-3DCA?can regulate the aggregates of C₁₂C₃C₁₂Br₂/SDS from spherical vesicles to rod-like aggregates.For C₁₂C₁₀C₁₂Br₂/SDS systems,Dex-3DCA was able to adjust the shape and size of the aggregates,while the free Na DCA was able to solubilize the membrane of vesicle to reduce the number of layers of multi-layer and multi-core vesicles.All the results will provide a deep insight into further investigation and developing application of these complex systems.Biocompatible bile salts and polymers modified with steroid structure have important theoretical and practical implications for functioning vesicle aggregates in the encapsulation and the triggered release of drugs.