title: A novel method for synthesizing PEGylated chitosan nanoparticles: strategy, preparation, and in vitro analysis.
abstract: Preparation of poly (ethylene glycol) (PEG)-grafted chitosan is essential for improving the biocompatibility and water solubility of chitosan. Presently available methods for this have limitations. This article describes a new method for preparing PEGylated chitosan nanoparticles. For this chitosan was chemoselectively modified using a novel scheme at the C6 position of its repeating units by PEG. The amine groups at the C2 position of the chitosan were protected using phthalic anhydride. Sodium hydride was used to catalyze the etherification reaction between chlorinated chitosan and methyl-PEG, and PEG-grafted chitosan was successfully synthesized. Each step was characterized using 13C nuclear magnetic resonance and Fourier transform infrared. After PEGylation the phthaloylated chitosan was successfully deprotected using hydrazine monohydrate. The synthetic scheme proposed demonstrates a new method for grafting PEG onto chitosan with a moderate degree of substitution. The potential of this polymer in nanoparticle preparation using an ionic gelation method and its gene delivery potentials were investigated by complexing a fluorescently labeled control siRNA. The result showed that suitable nanoparticles can be synthesized using this polymer and that they have capacity to carry genes and provide adequate transfection efficacy with no toxicity when tested in neuronal cells.
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, Quebec, Canada.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Malhotra
authors.forename: Ciaran
authors.initials: C
authors.lastname: Lane
authors.forename: Catherine
authors.initials: C
authors.lastname: Tomaro-Duchesneau
authors.forename: Shyamali
authors.initials: S
authors.lastname: Saha
authors.forename: Satya
authors.initials: S
authors.lastname: Prakash
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D024202:Electrophoretic Mobility Shift Assay; D018014:Gene Transfer Techniques; D008567:Membranes, Artificial; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D019906:Nuclear Magnetic Resonance, Biomolecular; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014162:Transfection / Q000379:methods
chemical_list: D008567:Membranes, Artificial; D011092:Polyethylene Glycols; D048271:Chitosan