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Synthesis and Evaluation of Supramolecular Nanostrutures of Cyclodextrin/Polyglycerol with Controlled Drug Delivery Applications

Zarrabi, Ali | 2011

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 42392 (48)
  4. University: Sharif University of Technology
  5. Department: Institute for Nanoscience and Nanotechnology
  6. Advisor(s): Vossoughi, Manouchehr; Adeli, Mohsen; Shokrgozar, Mohammad Ali
  7. Abstract:
  8. Today, human is facing and struggling with one of the most deadly disease, Cancer. Accordingly, several research studies are aimed to develop new anticancer drugs. Among the prescribed drugs are Paclitaxel. Unfortunately, despite the anticancer activity, paclitaxel has very low water solubility. To solve this problem several alternatives have been proposed by researchers, e.g. using co-solvents of ethanol:Cremophor El®, as is the case in commercial drug, Taxol®. Unfortunately, these co-solvents have some dangerous and sometimes mortal side effects. To reduce its side effects, researchers have proposed using cyclodextrin as a carrier for paclitaxel on the basis that cyclodextrin has a hydrophilic exterior and hydrophobic interior side. It is shown in literature that cyclodextrin derivatives could increase the solubility of hydrophobic moieties more than bare cyclodextrin. In this research, biocompatible polyglycerol was chosen for conjugation to cyclodextrin (β-CD-g-PG). Different characterization methods such as NMR, GPC, DSC and DLS were carried out to evaluate the conjugation, mean molecular weight, thermal behavior and particle size. The synthesized nanostructure was 10 nm in size and had a narrow molecular weight distribution. The hydrophobic moiety encapsulation was evaluated by encapsulating Ferrocene and FITC. Due to large amount of surface functional group and the encapsulation ability, β-CD-g-PG was introduced as a novel carrier for drug delivery. To this end, the carrier should be biocompatible. Therefore, several in vitro and in vivo biocompatibility tests were done. These tests confirmed the cellular and blood biocompatibility of β-CD-g-PG. In order to achieve the novel anticancer nanomedicine formulation, complexation between paclitaxel and β-CD-g-PG was investigated using NMR, DSC and FTIR methods. Optimization results for complexes with different ratios of drug to nanostructure showed that the 1:20 ratio had the highest drug loading. Circular dichroism spectroscopy revealed that the drug structure which could influence its activity is preserved even after complexation. Eventually, the anticancer efficacy of this novel formulation was evaluated against breast cancer cell line (MCF-7) and prostate cancer cell line (DU-145). The promising results showed reasonable anti-cancer efficacy while eliminating side effects of co-solvents
  9. Keywords:
  10. Polyglycirol ; Pacli Taxel (PTX) ; Biocompatibility ; Beta-Cyclodextrin ; Cancer ; Host-Guest Complex ; Nanomedicine

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