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Study on the structure and properties of ordered aggregates of Curcumin

Author: GuoFuMin
Tutor: WangZhongNi
School: Shandong Normal University
Course: Physical and chemical
Keywords: Curcumin Lyotropic Liquid Crystal Microemulsion Rheology SmallAngle X-ray Scattering Drug Carrier Stability Antioxidation
CLC: TQ460.1
Type: Master's thesis
Year: 2014
Downloads: 1
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Abstract

Rheological properties and microstructures of lyotropic liquid crystals formed bymixtures of Brij97, S1570and IPM in different midia: water and aqueous solution ofPEG400were studied by means of rheological methods and Small Angle X-rayScattering Technique(SAXS). Curcumin was solubilized into the lyotropic liquidcrystals formed in the two systems above in order to study the rheological properties,microstructures, light stability, and controlled release of curcumin-loaded surfactantaggregates. Microemulsion formed by Brij97/isopropanol/ethyl acetate/water systemwas built. Curcumin was also solubilized into the microemulsion system to study thelight stabity, thermal stability and antioxidant activity of drug-loaded microemulsion.This paper is intended to a certain reference value and significance on application ofcurcumin carrier and contains the following three parts:1. The research status of curcumin preparations and the advantageof ordered surfactant aggregates as drug carrier.Curcumin is natural antioxidant with very high safty which has been widely used inbiology and pharmacology. But the curcumin has low solubility in water, decomposedeasily when irradiated or heated and is unstable in environment with alkaline andneutral pH. These factors resulted in its low bioavailability. Therefore, drug carrierswhich are safe, reliable and have biological conservation function are needed toovercome the defects of curcumin on drug application. The aim of curcuminpreparation is to increase the solubility of curcumin, prevent the curcumin frominactivation by hydrolysis, keep curcumin sustained release and even help targetedrelease. Common carrier or formulation mainly includes: liposome, polymernanoparticles, polymer micelle, cyclodextrin and solid dispersion, etc. Surfactantordered assemblies are widely existed in cell membranes and organs such asbiological tissues. Common organized surfactant assemblies are micelle,microemulsion, vesicle, lyotropic liquid crystal, etc. Thees aggregates have good application prospects in drug carrier. Ordered surfactant aggregates as drug carrier hasthe following advantages:(1) They can significantly improve the solubility of poorlywater-soluble drug;(2)They can make the drug has good release effect;(3) They havethe good targeting properties.2. Build of curcumin-loaded lyotropic liquid crystals and studies oftheir performance.Phase behaviors Brij97-S1570/IPM in different media: water and10%PEG400aqueous solution were studied at37oC. The liquid crystalline phases in both systemscontain one lamellar (Lα) and one cubic (I) phase. Liquid crystalline phases in watersystem solubilize up to37.5wt%IPM at a water content ranging from16to52.5wt%.Liquid crystalline phase in water-PEG400system gets shrinked but dissolves moreIPM up to45.5wt%. All the samples in water system and PEG400system exhibitnon-Newtonain behavior with shear-thinning properties and suffer shear-thickening atintermediate shear rate. γcwhere the viscosity starts increasing get increased as thewater (or PEG400aqueous solution)content increases. Besides, γcbecomes higherand the σygets lower in the presence of PEG400in comparition with those of watersystem. SAXS results showed that studied lamellar structures in water system weremixed with some nonlamellar structures. The addition of PEG400can make thenonlamellar structures disappeared and leading to more ordered structures.When curcumin was added in to Brij97-S1570/IPM/water and Brij97-S1570/IPM/water-PEG400systems，η0.013, γc, σc, σy, S and|m|all have anincreasing tendency. The storage modulus (G′) and the loss modulus (G′′)get muchhigher and the increase is much more pronounced for both systems when curcumin isonly solubilized in IPM. This could be due to that the curcumin can help theformation of nonlamellar structures which may contribute to the increment in G′andG′′.Light stability experiments showed that the lyotropic liquid crystals havesignificant protective effect on curcumin. Drug release experiments showed thatbalance time of release extended obviously when curcumin was solubilized in lyotropic liquid crystal. The release followed the zero-order release kinetics at theearly stage and followed the first-order release kinetics at the later stage.3. Build of curcumin-loaded microemulsion and studies of itsperformance.Microemulsion formed by Brij97/isopropanol/ethyl acetate/water system was built.Curcumin was solubilized into the microemulsion system to study the light stabity,thermal stability and antioxidant activity of drug-loaded microemulsion.When themass ratio of surfactant to cosurfactant equals1:1, a big microemulsion area appearsin Brij97/isopropanol/ethyl acetate/water system. When the water content is lowerthan54%, oil in water microemulsion appears. When the water content is between54%and65%, bicontinuous microemulsion appears. While when the water content ishigher than65%, water in oil microemulsion appears.Stability test showed that the microemulsion plays a protective role on curcuminand can improve its light stabity and thermal stability.The survival rate of curcumin inmicroemulsion is high to90%after save for1hour at85oC. Under the natural light,drug content in the the curcumin microemulsion is close to50%after250hours,which is two times higher than that in ethyl alcohol.Oxidation experiments showed that oil in water microemulsion in Brij97/isopropanol/ethyl acetate/water/curcumin system could give significant scavengingeffects onO2. When the mass ratio of mixed surfactants to ethyl acetate equals9:1,the oil in water microemulsion shows the best antioxidant effect with IC50=17ug/mL.

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