PEGylation of chitosan via nitroxide chemistry in aqueous media
May 10-15, 2015
Chitosan (CTS) is one of the most important biopolymers on earth, and is derived from the second most abundant natural polymer, chitin. CTS, valued for its biocompatibility, biodegradability, and biological tolerance, finds applications in the biomedical and pharmacy fields including for example with drug delivery systems.1-5 However its properties and applications in such fields can be improved if functional groups or polymer chains are covalently attached to modify its properties. PEGylation of CTS has been used to enhance CTS solubility, biocompatibility and absorption since it has low toxicity and is biocompatible.6-7 In this research, PEGlytation of CTS with well-defined poly(poly(ethylene glycol) methyl ether methacrylate), polyPEGMA, via nitroxide chemistry and a “grafting to” approach is reported for the first time. To achieve PEGylation of CTS, CTS was first functionalized with glycidyl methacrylate (GMA) yielding CTS-g-GMA. Nitroxide-terminated polyPEGMA was polymerized via nitroxide-mediated polymerization (NMP) in water at 90 ºC using 2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (VA-044) as initiator and N-tert-butyl-N-(1-diethylphosphono-2,2-dimethylpropyl) nitroxide (SG1) as nitroxide. PolyPEGMA chains were then grafted to CTS-g-GMA in aqueous media, yielding CTS-g-GMA-PolyPEGMA. The synthesis of CTS-g-GMA-PolyPEGMA was confirmed by 1H NMR, TGA and FT-IR. A further unique feature of our research is that both the graft polymer synthesis and “grafting to” step were performed in aqueous media, thereby avoiding the use of toxic solvents.
1. M. N. V. Ravi Kumar, Reactive and Functional Polymers, 2000, 46, 1-27. 2. M. Rinaudo, Progress in Polymer Science, 2006, 31, 603-632. 3. M. Rinaudo, Polymer International, 2008, 57, 397-430. 4. H. Sashiwa and S.-i. Aiba, Progress in Polymer Science, 2004, 29, 887-908. 5. H. Yi, L.-Q. Wu, W. E. Bentley, R. Ghodssi, G. W. Rubloff, J. N. Culver and G. F. Payne, Biomacromolecules, 2005, 6, 2881-2894. 6. H. Hussain, K. Y. Mya, C. He, Langmuir : the ACS journal of surfaces and colloids 2008, 24, 13279–13286. 7. F. M. Veronese, G. Pasut, Drug Discovery Today 2005, 10, 1451–1458.