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Design and Fabrication of Drug-loaded Nanoparticles to Prevent Fibrillation of Alpha-synuclein in Parkinson

Nayebzadeh, Ramin | 2015

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 47524 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Mashayekhan, Shohreh; Morshedi, Dina
  7. Abstract:
  8. The purpose of this study is to assess the inhibitory effects of an appropriate nanoparticles loaded with gallic acid on the fibrillation of alpha-synuclein. Alpha-synuclein is a major component of protein plaques in synucleinopathies, particularly Parkinson’s disease. Gallic acid (GA, 3,4,5-trihydroxy benzoic acid) is a well–known small molecule which can inhibit the formation of α-synuclein fibrils. For the process of fibrillation, purified protein was incubated at 37◦C and pH 7.2. Fibrillation was analyzed by the standard fibril methods.after that investigated fabricating of gallic acid trapped in the chitosan nanoparticles and gallic acid loaded in chitosan –coated mesoporous silica nano-particles . The prepared nanoparticles were characterized by electron microscopy and Dynamic light scattering. Drug loading and entrapment efficiency of chitosan nanoparticles and chitosan –coated mesoporous silica nano-particles (Ch-A-MSNs) were examined with UV spectroscopy. The release of gallic acid from nanoparticles was also assessed in an aqueous solution via spectrophotometry. The process of a-Syn fibril formation was monitored by Thioflavin T (ThT) assay, atomic force microscopy (AFM) and fluorescence microscopy imaging. MTT assay was employed to evaluate the cytotoxicity effects and of a-Syn fibrils on a PC12 cell line in the absence and presence of nanoparticles. The gallic acid trapping in chitosan nanoparticle results indicated that chitosan nanoparticles wasn’t appropriate nanocarier because of low gallic acid trapping and high aggregation. Our results showed that the fibril formation is reduced considerably in the presence of gallic acid-loaded Ch-A-MSNs, and it was also demonstrated that increasing the concentration of the drug-loaded nanoparticles (NPs) results in greater effects on the fibril formation inhibitingso that inhibited fibrillation by more than 80% without any toxit effect on PC12 cell. Subsequently, the cytotoxicity of the incubated alpha-synuclein proteins was noticed to be significantly reduced in the presence of gallic acid-loaded Ch-A-MSNs in comparison to that in the absence of these drug-loaded NPs
  9. Keywords:
  10. Nanoparticles ; Parkinson Disease ; Nanocarrier ; Protein Fibrillation ; Alpha Synuclein ; Small Mole Cules ; Gallic Acid

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