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Design of Oxidative Stress Nanoparticles for Targeted drug Delivery to the Posterior Segment of the Eye and Breast Cancer

Behroozi, Farnaz | 2018

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 51018 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Abdekhodaei, Mohammad Jafar; Baharvand, Hossein; Satarian, Leila; Sadeghi, Hamid
  7. Abstract:
  8. The oxidation-reduction (redox) responsive micelle system is based on a diselenide-containing triblock copolymer, poly(ε-caprolactone)-bis(diselenide-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate) [PCL-(SeSe-mPEG/PEG-FA)2]. Resulting in the development of tumor-targeted delivery for hydrophobic anticancer drugs. The diselenide bond, as redox-sensitive linkage, was designed, so it is located at the hydrophilic/hydrophobic hinge to allow complete micelles collapse and efficient drug release, in redox environments. The amphiphilic block copolymers self-assembled into micelles at concentrations above the critical micelle concentration (CMC) in an aqueous environment. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses showed that the micelles were spherical with an average diameter of 120 nm. The insoluble anti-cancer drug paclitaxel (PTX) was loaded into micelles and its triggered release behaviour under different redox conditions was verified. Folate-targeting micelles showed an enhanced uptake in 4T1 breast cancer cells and in vitro cytotoxicity by flow cytometry and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium) (MTS) assay, respectively. Delayed tumor growth was confirmed in the subcutaneously implanted 4T1 breast cancer in mice after intraperitoneal injection. The proposed redox-responsive co-polymer offers a new type of biomaterial for delivery of drug to cancer in vivo
  9. Keywords:
  10. Drug Delivery ; Breast Cancer ; Micelle ; Nanocarrier ; Targeted Druy Delivery ; Retina ; Oxidative Stress ; Smart Nanocarriers

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