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.

Keywords:

• nanoparticles
• chitosan
• poly (ethylene glycol)
• polymeric membrane
• gene delivery

Acknowledgements

The authors would like to acknowledge the Canadian Institutes of Health Research (CIHR) grant (MOP-93641) to Dr S Prakash, the support of McGill Major Scholarship to M Malhotra, the support of Industrial Innovation Scholarship (IIS) BMP Innovation – NSERC, FQRNT scholarship and Micropharma Limited Scholarship to Catherine Tomaro-Duchesneau. We would like to acknowledge the support of the Centre of Biorecognition and Biosensors, the NMR Facility at Quebec/Eastern Canada High Field NMR Center, the Centre for self-assembled Chemical Structures (CSACS) and the facility of Electron Microscopy Research at McGill University. We would like to acknowledge the guidance of Dr Hani Al-Salami for statistical analysis.

Disclosure

The authors declare no conflicts of interest.