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Fabricate of Novel Drug Vector Based on Metallic Nanoparticles and Study of its Effects on Cell Line

Asadishad, Bahareh | 2010

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 40527 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Vosoughi, Manouchehr; Alemzadeh, Iran
  7. Abstract:
  8. Application of nanoparticles in targeted delivery and controlled drug release is recently highly attracted especially in cancer therapy. In this study with the aim of developing a novel drug vector based on metallic nanoparticles, gold nanoparticles with their unique characteristics were used to design a vector for targeted anti-cancer drug delivery to tumor. First, gold nanoparticles were chemically synthesized therough sodium citrate and sodium brohydrate reductions with average diameters of 22 and 11 nm, respectively. Then, the activated poly ethylene glycol (PEG) and activated folic acid were conjugated to the lysine-capped gold nanoparticles. Subsequently, the widely used anticancer agent doxorubicin (DOX) was successfully attached to the surface of folate-modified, PEG-functionalized gold nanoparticles. Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and UV/vis spectrometer were used to cofirm the functionalization and conjugation steps in the chemical synthesis. Activated PEG was also characterized wth NMR, GPC, and MALDI-TOF mass analysis. The DOX-loading efficiency determined by UV.vis spectrometer was 80%. Drug release experiments followd a Higuchi matrix model. DOX nanocarries showed higher cytotoxic effect on folate-receptor-positive cells (KB cells) than folate-receptor-negative cells (A549 cells). Cell viability in healthy cells (HFF cells) in drug-loaded nanoparticles was higher compared to free doxorubicin. These nanocarriers might offer a cancer therapy with high targeting efficiency and lower side effects
  9. Keywords:
  10. Gold Nanoparticle ; Polyethylen Glycol (PEG) ; Folic Acid (FA) ; Drug Delivery ; CONTROLLED RELEASE ; Doxorubicin

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