Formation Of Natural Amphiphilic Associated Structures And Their Protective Effects On Drugs

The influence of soybean lecithin (SL) on the Brij97/castor oil (COil)/H2O system was studiedfirst by phase diagram method and polarization experiment. The rheological properties andmicroscopic structure of these systems were then investigated through the rheological and smallAngle X-ray scattering method. Then took the drug excipients isopropyl ester (IPM) and theethyl oleate (EtOL) security to the body as oil phase, the comparative study of IPM, EtOL andCOil in SL/Brij97(1:1)/H2O system properties was studied. In addition, in order to furtherincrease the solubilization ability of curcumin, the effect of propylene glycol which has goodsolubilization capacity of curcumin was studied on the lyotropic liquid crystal formed bySL/COil/H2O system. Finally, the application of the lyotropic liquid crystals got from the abovesystems used as a carrier of drugs, including the release behavior and stability of curcumin wasstudied, respectively. The work will have important guiding significance in the aspect of foodindustry and pharmaceutical development. This paper mainly includes the following fourchapters:1. IntroductionOn the basis of consulting a large number of domestic and foreign literatures, the researchstatus of the aggregates formed by amphiphilic molecules including the lecithin as the mainsurfactant, and their protection of them as a drug carrier was summaried. We mainly introducedthe research progress of lyotropic liquid crystal used as drug carrier formed by amphiphilicmolecules, including micelle, vesicle/liposome, microemulsion, and lyotropic liquid crystal andthe research of microemulsion, vesicles and lyotropic liquid crystal formed by lecithin solution.Through the above literature review, we found that lecithin, as a kind of natural surfactant,non-toxic, no stimulation, good biocompatibility, and can form a variety of aggregates structure,having good advantages in terms of doing drug carrier. And in addition to the required non-toxicof drug carrier, on the other hand it is important that how to increase the drug solubilizationability. So it put forward higher requirements on how to select components. Therefore lecithinforms aggregates structures and the application in drug carrier is a trend in future research. Basedon this, we selected the natural amphiphilic molecule lecithin as the main surfactant, and carriedout the following research content in this work. 2. The formation of aggregates by SL/Brij97/Coil/water systems andtheir protection for curcuminIn this chapter, the phase diagrams of Brij97/castor oil (COil)/water at the present of soybeanlecithin (SL) were determined at37oC. The liquid crystalline phases were investigated by meansof polarizing optical microscopy (POM), rheological technique and small angle X-ray scattering(SAXS). With an increase in SL content, the domain of lamellar phase becomes larger andextends to higher COil concentration. At the constant surfactant concentration, the shearviscosity of lamellar phases gets larger for samples containing more SL. The storage modulus G’of lamellar phase gets increased by the addition of SL and get a maximum in SL/COil/watersystem, which is related to the smallest area of surfactant molecules at the interface (aS). ForBrij97/SL (1:3) system, at a fixed ratio of COil/water, the dynamic moduli get increased withincreasing surfactant concentration. The release and stability experients show that LCs can slowthe release rate and improve the stability of curcumin.3. The formation of aggregates by SL/Brij97(1:1)/oil/water systems andtheir protection for curcuminIn this chapter, a further study on the Brij97/SL (1:1)/water/oil (COil, EtOL, IPM) systemswas made with different oil component. The phase diagrams of Brij97/SL (1:1)/water/oil systemswere determined at37oC. The liquid crystalline phases were investigated by means of polarizingoptical microscopy (POM), rheological technique and small angle X-ray scattering (SAXS). It isshown that at a given temperature (37oC), the ethyl oleate (EtOL) and COil systems have thehigher moduli and the smaller area of surfactant molecules at the interface than the isopropylmyristate (IPM) system. Temperature effect investigations also indicated that the values ofactivation energy, Ea, of samples in this study are higher than the lamellar phase reported inSynperonic A7system. In addition, the Ea of EtOL and COil systems are larger than that of IPMsystem. These may imply that the stronger network strength of the lamellar phases especially in EtOL and COil systems. From the release and stability experients, we can see that release ratebecome slower and stability is improved of curcumin in LCs.4. The formation of aggregates by SL/Coil/water/PG systems and theirprotection for curcuminThe phase diagrams of soybean lecithin (SL)/castor oil (COil)/water at the present of1,2-propylene glycol (PG) were determined at37oC. The liquid crystal (LC) phases wereinvestigated by means of phase diagram, polarization microscopy (POM), small angle-X rayscattering (SAXS) and rheological technique. With an increase in PG content, the area of LCdomain decrease. SAXS measurements were performed to determine the difference in LCstructure. For SL/COil/water system, as the COil content increase, the radius of the hydrophobicpart of the cylinders (dH) values of typical hexagonal samples with the same surfactant contentincrease and area per surfactant at the interface (aS) get decreased. After adding PG to the LCsamples not containing oil, they transform into lamellar structure. But the hexagonal structure forthe samples containing COil has not changed. With an increase in COil content, the values of dHincrease and aSget decreased. And the increase of PG leads to the increase of aSat fixedsurfactant content, while the trend in distance between the cylinders (dW) is in reverse order. Forthe samples dissolved curcumin, with H2O/PG ratios1/0,7/3,5/5, the dHvalues decrease and aSincrease compared to the empty drug-loaded samples, respectively. But when H2O/PG ratio is3/7, dHincreases and aSgets a slight decrease compared to empty drug sample. These are inaccordance with the results of rheological measurements. Oscillatory measurements show all thesamples possess gel-like fluid behavior. In each system, the shear viscosity and dynamic moduli(G’ and G″) increase with the COil content increasing at constant surfactant. But the adding ofPG, which can reduce the interaction strength among the rod-shaped aggregates of the hexagonal phase, decreases the dynamic moduli of the system. Besides, when the COil and PG weredissolved curcumin, the dynamic moduli first is smaller and then bigger than the empty sampleswith an increase in PG content. This may be the result of the combined action caused bycurcumin located in the different position in LC samples. From the release and stabilityexperients, we can see that the release rate become slower and stability is improved of curcuminin LCs. So LCs have a protective effect of drug.