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Preparation and Evaluation of Nanopolysaccharides- & Polysaccharides-Anticancer Drugs Conjugates

Akhlaghi, Mehdi | 2012

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 43316 (03)
  4. University: Sharif University of Technology
  5. Department: Chemistry
  6. Advisor(s): Pourjavadi, Ali
  7. Abstract:
  8. In recent years, cancer is the second leading cause of human death. Cancer treatment is based on surgery, chemotherapy and radiation therapy. Choice of treatment method depends on the degree of progression and type of cancer. However, the goal is destruction of cancer cells and minimal harmful side effects on healthy cells. In this thesis two types of polysaccharide-anticancer drug conjugate were prepared and evaluated for radiation therapy and chemotherapy; chitosan- and DTPA modified chitosan – Gallium 66 conjugates for radiation therapy and nano diacid starch –cisplatin conjugate for chemotherapy. Chitosan –gallium 66 conjugate was prepared in radiochemical purity higher than 99% at optimal condition considering the effect of concentration and pH of chitosan solution and then injected intratumoral to mice. 54 h post injection, 14/6% of injected radioactivity leaked from injection site and uptake in liver and lungs. However, after modification of chitosan by DTPA, as a complexing agent, the stability of DTPA chitosan-gallium 66 conjugate increased and just 2.7% of injected radioactivity leaked form injection site after 54 h post intratumoral injection of DTPA chitosan-gallium 66 conjugate with radiochemical purity higher than 99% prepared in optimal condition. In the next section of thesis, diacid starch nanoparticle was prepared by alternative oxidation with NaIO4, NaClO2 and H2O2 followed by crosslinking with OPCl3 in oil-water emulsion medium. Nanoparticle-cisplatin conjugate was prepared in aqua medium and loading behavior of drug was evaluated in several feedings cisplatin / nanoparticle (w/w) ratio. After in-vitro drug release evaluation, the conjugate was injected to mice and blood platinum concentration was measured by time. The result showed longer nanoparticle-cisplatin conjugate blood circulation compared to cisplatin.
  9. Keywords:
  10. Chitosan ; Polysacharide-Anticancer Drugs Conjugate ; Intratumor Radiotherapy ; Gallium-66 ; Diacid Starch Nanoparticles ; Cisplatin

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