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Selective Transfection of Smart Polymeric Nanoparticles Into Reactive Astrocytes in Animal Model of Spinal Cord Injury

Sabourian, Parinaz | 2021

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 54657 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Frounchi, Masoud; Mashayekhan, Shohreh; Kiani, Sahar
  7. Abstract:
  8. In this study, chitosan-based nanoparticles were prepared due to their biocompatibility, availability, high loading capacity of drug, stimulus responsive behavior and the presence of active functional groups. Chitosan was chemically functionalized with reactive oxygen species (ROS)-responsive moiety to respond to the oxidative stess and endosomal pH in nerve injuries. To prepare nanoparticles, functinalized chitosan ionically gelated with pH-responsive polyanions with ROS-scavenging properties such as polyacrylic acid and hyaluronic acid. Then, pH- and ROS-responsive nanoparticles were used for selective transfection into reactive astrocytes and axonal regeneration in spinal cord injuries. For this purpose, nanoparticles were electrostatically modified with a targeting ligand (lipopolysaccharide) to selectively transfect into reactive astrocytes through possible ligand-receptor interactions both in vitro and in spinal cord injured rat. To evaluate versatility and therapeutic effects of smart nanoparticles, they were separately loaded with quercetin (as a hydrophobic drug) and nerve growth factor. Sustained drug release and improved neurite out-growth were observed in explanted mouse dorsal root ganglia. In vitro studies showed that pH-responsive nanoparticles with optimal physico-chemical properties swelled in the mimicked acidic environment of endosomes and entered the cytosols and nuclei of cells. Nanoparticle’s internalization into the nuclei, indicated their high chemical stability in the physiological environment. It can be concluded that chitosan-based smart polymeric nanoparticles are desired alternatives for unsafe viral vectors in targeting reactive astrocytes and releasing the growth, differentiation and repair factors in spinal cord injuries
  9. Keywords:
  10. Chitosan ; Polymeric Drug Nanoparticles ; Selective Transport ; Reactive Astrocytes ; Nerve Injury ; Biocompatibility ; Reactive Oxygen Species (ROS)

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