O-Alkylation of Chitosan for Gene Delivery by Using Ionic Liquid in an in- situ Reactor


An in-situ reactor was elaborately designed for O-alkylation of chitosan in an ionic liquid ([BMIM]Cl) solvent, using N, N'-carbonyldiimidazole  as bonding agent. The original chitosan and the modified chitosan were characterized by FT-IR and XRD analysis. FT-IR spectra revealed that the alkylation of chitosan selectively occurred at hydroxyl groups, with unprotected amino groups untouched. It was proposed that the particular properties of the ionic liquid solvent should be responsible for the selectively alkylation. The result from X-ray diffraction showed that the crystallinity of O-alkylation of chitosan decreases, most likely due to the decomposition of CS in the ionic liquid. The solubility test of O-alkylated chitosan in aqueous HAc solution (w/w: 0.1%) confirmed that the product could be easily dissolved in aqueous HAc solution because of its abundant free amino groups. It was suggested that the O-alkylated chitosan was suitable for the coming cell transfection test in vitro.

Share and Cite:

H. Chen, S. Cui, Y. Zhao, B. Wang, S. Zhang, H. Chen and X. Peng, "O-Alkylation of Chitosan for Gene Delivery by Using Ionic Liquid in an in- situ Reactor," Engineering, Vol. 4 No. 10B, 2012, pp. 114-117. doi: 10.4236/eng.2012.410B029.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] G. Hellermann, S. S. Mohapatra, “Genetic therapy: on the brink of a new future,” Genet. Vaccines Ther., 2003, vol. 4, pp. 1-9.
[2] M. Breunig, U. Lungwitz, R. Liebl, A. Goepferich, “Breaking up the correlation between efficacy and toxicity for nonviral gene delivery,” Proc. Natl. Acad. Sci. U.S.A. 2007, vol. 104, pp. 14454–14459.
[3] H. T. Lv, S. B.Zhang, B. Wang, S. H. Cui, J. Yan, “Toxicity of cationic lipids and cationic polymers in gene delivery,” J. Controlled Release , 2006, vol. 114, pp. 100–109.
[4] D. Luo, M. Saltzman, “Synthetic DNA delivery systems,” Nat. Biotechnol., 2000, vol. 18, pp. 33-37.
[5] J. M. Dang, K. W. Leong, “Natural polymers for gene delivery and tissue engineering,” Adv. Drug Delivery Rev., 2006, vol. 58, pp. 487–499.
[6] S. Mansouri, P. Lavigne, K. Corsi, M. Benderdour, E. Beaumont, J. C. Fernandes, “Chitosan/pDNA nanoparticles as non-viral vectors in gene therapy: strategies to improve transfection efficacy,” Eur. J. Pharm. Biopharm., 2004, vol. 57, pp. 1-8.
[7] K. Bowman, K. W. Leong, “Chitosan nanoparticles for oral drug and gene delivery,” Int. J. Nanomed., 2006, vol. 1, pp. 117–128.
[8] K. Y. Lee, “Chitosan and its derivatives for gene delivery,” Macromol.Res., 2007, vol. 15, pp. 195–201.
[9] O. Germershaus, S. R. Mao, J. Sitterberg, U. Bakowsky, T. Kissel, “Gene delivery using chitosan, trimethyl chitosan, or polyethylenglycol graft-trimethyl chitosan block copolymers: establishment of structureactivity relationships in vitro,” J. Controlled Release, 2008, vol. 125, pp. 145–154.
[10] M. Kurisawa, M. Yokoyama, T. Okano, “Transfection efficiency increases by incorporating hydrophobic monomer units into polymeric gene carriers,” J. Controlled Release, 2000, vol. 68, pp. 1-8.
[11] T. Sato, T. Kawakami, N. Shirakawa, Y. Okahata, “Preparation and characterization of DNA-lipoglutamate complexes,” Bull. Chem. Soc. Jpn., 1995, vol. 68, pp. 2709-2715.
[12] A. V. Kabavov, V. A. Kavanov, “DNA complexes with polycations for the delivery of genetic materials into cells,” Bioconjugate Chem., 1995, vol. 6, pp. 7-20.
[13] W. G. Liu, X. Zhang, S. J. Sun, G. J. Sun, K. D. Yao, “N-Alkylated Chitosan as a Potential Nonviral Vector for Gene Transfection,” Bioconjugate Chem., 2003, vol. 14, pp. 782-789.
[14] P. S. Kuhn, Y. Levin, M. C. Barbosa, “Charge inversion in DNA-amphiphile complexes: possible application to gene therapy,” Physica. A, 1999, vol. 274, pp. 8-18.
[15] C. Cuissinat, P. Navard, T. Heinze, “Swelling and dissolution of cellulose, Part V: Cellulose derivatives fibres in aqueous systems and ionic liquids,” Cellulose, 2008, vol. 15, pp.75–80.
[16] R. P. Swatloski, S. K. Spear, J. D. Holbrey, R. D. Rogers, “Dissolution of cellulose with ionic liquids,” Journal of the American Chemistry Society, 2002, vol. 124, pp. 4974–4975.
[17] H. Zhang, J. Wu, J. Zhang, J. S. He, “1-Allyl-3-methylimidazolium chloride room temperature ionic liquid: A new and powerful nonderivatizing solvent for cellulose,” Macromolecules, 2002, vol. 38, pp. 8272–8277.
[18] H. B. Xie, S. B. Zhang, S. H. Li, “Chitin and chitosan dissolved in ionic liquids as reversible sorbents of CO2.,” Green Chemistry, 2002,vol. 8, pp. 630–633.
[19] R. P. Swatloski, S. K. Spear, J. D. Holbrey, R. D. Rogers, “Dissolution of cellulose with ionic liquids,” Journal of the American Chemical Society, 2002, vol. 124, pp. 4974–4975.
[20] H. Susanne, F. Ralf, H. Andreas, S. Frank, “Hydrophobic Chitosan Microparticles: Heterogeneous Phase Reaction of Chitosan with Hydrophobic Carbonyl Reagents,” Biomacromolecules, 2007, vol. 8, pp. 2051-2058.
[21] F. Feng, Y. Liu, B. Y. Zhao, K. Hu, “Characterization of half N-acetylated chitosan powders and films,” Procedia Engineering, 2012, vol. 27, pp. 718-732.
[22] Z. H. Zhang, C. Z. Li, Q. Wang, Z. B. Zhao, “Efficient hydrolysis of chitosan in ionic liquids Carbohydrate Polymers,” Carbohydrate Polymers, 2009, vol. 78, pp. 685-689.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.