| Nowadays, under the background of increasing concern about environmental pollution in theworld, biosurfactant, a kind of green surfactant with low toxicity, high biodegradability, goodbiocompatibility and biological activities, has attracted more and more interest of researchers.Bile salts have a rigid facial structure which exhibits amphiphilic and chiral properties.Meanwhile, as a kind of biosurfactant, bile salts have some advantages such as low toxicity,good biocompatibility and biodegradability. The construction and regulation of bile saltsaggregate are different from conventional surfactants. Therefore, taking bile salts as the researchobject to construct aggregation which can be used as drug delivery may provide a theoreticalbasis for food industry, biotechnological and pharmaceutical development. This paper mainlyincludes the four chapters as follows,(1) Initially, the nature and classification of biosurfactant is understood by consulting therelevant materials. Afterwards, the current state of research about surfactant assemblies as drugdelivery is summarized. Based on the combination of our studies and relevant literatures, thephysiological functions, structural features and the aggregation properties of bile salts aresummed up. It can be found that, with a specific structure, the self-assembly behavior of bilesalts is complex. In consequence the ability of bile salts to construct the lyotropic liquid crystaland the stability of aggregate can be improved by mixed with other surfactants, which couldresult in rich phase behavior of bile salt system, the enhanced thermal stability and shorterprocedure to get equilibrium. Therefore, this paper takes sodium deoxycholate (NaDC) as theresearch subject, which is mixed with nonionic surfactant Brij97to form NaDC/Brij97mixture.As a kind of drug excipients which are belong to FDA, IPM and PEG400are introduced intoNaDC/Brij97mixture to construct organized assemblies of this multiple content system. Themicrostructure and rheological properties of constructed aggregate are studied. Subsequently,drugs with poor stability and low bioavailability could be incorporated into these organizedassemblies and the properties of drug encapsulated aggregate as drug carrier will be studied. Thisis expected to be applied in the drug delivery system and will provide important guidingsignificance for the development of biotechnology and pharmaceutical fields.(2) The phase diagram of five components Brij97-NaDC/IPM-PEG400/H2O system wasdetermined at25oC. The hexagonal liquid crystalline phase (H1) and cubic phase (Fd3m) were found in this system. By use of small angle X-ray scattering (SAXS), polarization microscope(POM) and rheology techniques, the influence of composition, temperature and addition ofcurcumin on H1phase was studied. It is shown that (1) the investigated hexagonal liquid crystalsexhibit a strong shear thinning behavior and viscoelasticity. The strength of the network of H1phase becomes weaker with increasing oil content.(2) The frequency dependent moduli of H1samples decrease as the temperature increases and the steady-state limiting viscosity of thehexagonal samples shows an Arrhenius-like dependence on temperature.(3) Samples in H1phasecontaining curcumin retained their organized hexagonal structure. The SAXS results show thatthe curcumin molecules may be solubilized both into the apolar core of cylinders together withIPM and in the polar domain coexisting with PEG400between the cylinders. When curcumin isencapsulated in samples with low oil content, there is a significant decrease in the frequencydependent moduli. The tendency of frequency behavior for samples incorporating curcumin as afunction of temperature is weakened.(4) The drug release behavior of curcumin encapsulatedhexagonal samples showed a first-order kinetic and a prolonged curcumin release was observed.(3) The rheological properties of cubic liquid crystals formed in the Brij97-NaDC/IPM-PEG400/H2O system were investigated. The influence of oil content, curcumin and the proportion ofPEG400on the rheological properties of cubic liquid crystals were studied and discussed. Thesteady and dynamic rheological properties of cubic liquid crystals were measured by TA-2000exrheometer at25oC. The investigation of rheological properties showed that the cubic liquidcrystals formed by Brij97/NaDC mixture exhibit a shear-thinning behavior and viscoelasticity.The viscosity and dynamic moduli of cubic liquid crystals decreased with the increasing oilcontent, which indicates the decayed ability of anti-shearing and stability. There was little effectof curcumin on the rheological properties of cubic liquid crystals. Curcumin encapsulated cubicliquid crystals retained the ability of anti-shearing and stability. The appearance of a minimumfor the relaxation spectra of samples loaded curcumin indicates that an elastic network is formed.Upon addition of PEG400, the viscosity of cubic liquid crystals decreased. While the largervalue of tan δ with higher content of PEG400demonstrates the decayed elastic characteristics.Furthermore, the melting temperature of cubic liquid crystals with higher content of PEG400toisotropic micelle solution turned lower. A sustained release of curcumin was observed in cubicsamples with different oil content. The release rate of curcumin encapsulated cubic liquid crystals with higher PEG400concentration was faster. The drug release behavior of curcuminencapsulated cubic samples showed a first-order kinetic.(4) The phase behaviors of Brij97-NaDC/IPM/H2O systems with different Brij97/NaDCratio were studied. There were four single-phase regions in all three systems. When the Brij97/NaDC ratio was set to be7:3or8:2, there were two kinds of isotropic microemulsion phases,one anisotropic hexagonal liquid crystalline phase and one isotropic cubic liquid crystalline.However, when the Brij97/NaDC ratio was changed to be9:1, one W/O microemulsion phasedisappeared and a large region of lamellar liquid crystalline phase was observed. With theincreasing Brij97/NaDC ratio, the regular variation can be observed in O/W microemulsionphase, cubic liquid crystalline and hexagonal liquid crystalline phase. Curcumin encapsulatedhexagonal and cubic samples with different Brij97/NaDC ratio exhibited a sustained release ofcurcumin. The drug loaded hexagonal samples with the smallest ratio (7:3) of Brij97/NaDCshowed the best ability to sustain the release of curcumin. While the release rate of cubicsamples incorporated curcumin with a higher ratio (8:2or9:1) of Brij97/NaDC was higher thanthat of curcumin loaded ethanol solution. From the point of drug release kinetics, the drugrelease behavior of curcumin encapsulated hexagonal and cubic samples was a kind of dispersioncontrolled first-order kinetic procedure. The ageing stability and light stability of curcuminencapsulated hexagonal samples formed by Brij97-NaDC/IPM/H2O system were studied. Theresult showed that samples with a Brij97/NaDC ratio of7:3performed the best stability.However, the light stability of curcumin encapsulated hexagonal samples formed by Brij97-NaDC/IPM/H2O system were relatively poor. Furthermore, the ageing stability and lightstability of curcumin encapsulated hexagonal samples formed by Brij97-NaDC (4/1)/IPM-PEG400(1/1)/H2O system were much better, which implied that the introduction of PEG400intothe aggregate could enhance the stability of curcumin. |
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