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Preparation Of ?-cyclodextrin Supramolecular Assembly Magnetic Nanocomposites And Research And Application In Drug Delivery Systems

Posted on:2018-06-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y H ZhouFull Text:PDF
GTID:1311330521451239Subject:Analytical Chemistry
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Chapter 1:In this chapter,the structure,properties,preparation methods,characterization,and surface functionalization methods of magnetic Fe3O4 nanoparticles?MNPs?were briefly reviewed.In addition,the structural and properties of the cyclodextrins were also briefly reviewed.Finally,the progress of drug delivery system based on magnetic Fe3O4 nanoparticles and cyclodextrin was reviewed.Chapter 2:The magnetic Fe3O4 nanoparticles coated with 3-aminopropyltriethoxysilane were combined with 6-O-tosyl-?-cyclodextrin and ?-cyclodextrin functionalized magnetic nanoparticles??-CD-MNPs?was achieved by layer-by-layer method.The characterization by transmission electron microscopy revealed ?-CD-MNPs having an average diameter of 12±2 nm and an average hydrodynamic diameter of 56.8 nm in aqueous solution by dynamic light scattering.?-cyclodextrin grafting was confirmed by Fourier-Transformed Infrared spectroscopy?FT-IR?.The uptake and release ability of ?-CD-MNPs was investigated using methylene blue as model drug by spectrophotometric method.The results showed that the uptake and release were greatly influenced by the pH value of dye solution,with a maximum loading capacity of 78.4 mg/g under pH = 8 at 25 °C,and the release was easily achieved at 73% within the first hour at physiological condition.The adsorption isotherms were examined by Langmuir and Freundlich models,the Langmuir model suggested the adsorption on ?-CD-MNPs as a mono-layer coverage.The ?-cyclodextrin functionalized Fe3O4 magnetic nanoparticles may have a wide variety of biomedical applications i.e.as nanocarriers for hydrophobic drugs for the sitespecific delivery under externally applied magnetic field.Chapter 3:The inclusion between curcumin and ?-cyclodextrin,methyl-?-cyclodextrin,hydroxypropyl-?-cyclodextrin and sulfobutyl-?-cyclodextrin respectively in phosphate buffer solution with pH = 2.02 were studied by fluorescence spectroscopy with the fixed curcumin concentration.The fluorescence intensity of curcumin was gradually increased when the concentration of ?-cyclodextrin or its derivatives was gradually increased,indicating the formation of inclusion complexes.The inclusion constants were also calculated by the double reciprocal method of fluorescence intensity.The results showed that the fluorescence enhancement effect was sulfobutyl-?-cyclodextrin> hydroxypropyl-?-cyclodextrin> methyl-?-cyclodextrin> ?-cyclodextrin in the phosphate buffer system at pH =2.02 at room temperature,and the inclusion ratio is 1: 1.The quantitative determination of curcumin was investigated by sulfobutyl-?-cyclodextrin fluorescence sensitization was discussed,and the linear range from 5.0×10-7 mol/L to 4.5×10-6 mol/L,and the detection limit as 1.2×10-8 M.Chapter 4:The functionalized magnetic nanoparticles?MNPs?of ?-Cyclodextrin??-CD?or its derivatives with high saturated magnetism were fabricated successfully by an effective grafting method.The characterization by TEM,FTIR,DLS,Zeta potential and VSM confirmed the structure and expected properties of carboxymethyl/hydroxypropyl/ sulfobutylether-?-CD functionalized magnetic nanocomposites?CM/HP/SBE-?-CDMNPs?.Furthermore,the uptake and release performance of the as-prepared nanocarriers for the hydrophobic anti-cancer drug curcumin was also investigated by spectrophotometry.The results revealed that the SBE-?-CD-MNPs possessed the highest loading and release capacity as compared with other two nano-carriers.Cellular uptake image suggested that SBE-?-CD-MNPs have crossed the cell membranes,suggesting that curcumin could be successfully delivered inside the cell by SBE-?-CD-MNPs nanocarrier.The assessment of cell toxicity revealed that SBE-?-CD-MNPs were non-toxic.The curcumin loaded SBE-?-CD-MNPs showed a high potential for killing the HepG2 cells.The as-prepared magnetic nano-carriers were expected to have a broader application in the field of biomedicine.Chapter 5:The ?-CD derivative?carboxymethyl/hydroxypropyl/sulfobutylether-?-CD?was modified with bromoacetic acid under acidic conditions by a simple esterification reaction.In the presence catalyst of 4-dimethylaminopyridine and dehydrating agent N,Ndicyclohexylcarbamate,?-CD derivatives were grafted onto the surface of MNPs.?-CD derivative functionalized MNPs with folic acid mediator was achieved by dehydration reaction between folic acid and ?-CD derivative.The uptake and release of curcumin by FA-CD-MNPs through inclusion complexation was also investigated.The results revealed that FA-SBE-?-CD-MNPs have higher uptake and release capabilities.Cellular uptake image showed that FA-SBE-?-CD-MNPs entered cells and curcumin could be successfully delivered inside cells through FA-SBE-?-CD-MNPs nanocarriers.The cell cytotoxicity was assessed,and FA-SBE-?-CD-MNPs show non-toxic.?-CD derivative functionalized magnetic Fe3O4 nanocarriers with folic acid mediators are expected to have a great application for the targeted drug delivery.
Keywords/Search Tags:?-Cyclodextrin and its derivatives, Magnetic Fe3O4 Nanoparticles, Folic Acid, Curcumin, Drug Delivery System
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