Characterisation of products from EDC-mediated PEG substitution of chitosan allows optimisation of reaction conditions.

Abstract

PEGylation is a common method use to modify the physiochemical properties and increase the solubility of chitosan (CHI). Knowledge of optimal reaction conditions for PEGylation of CHI underpins its ongoing use in nanomedicine. This study synthesised methoxy polyethyleneglycol grafted CHI (mPEG-CHI) using carbodiimide-mediated coupling. The effect of reagent concentrations and pH on the degree of substitution (DS) and the PEGylation yield (conversion of free PEG to conjugated PEG) was evaluated through detailed chemical characterisation. Within the parameter space investigated, optimised reaction conditions (NH2: COOH:NHS:EDC of 3.5:1:1:10, pH = 5) resulted in a DS of 24 % and a PEGylation yield of 84 %. An EDC-derived adduct formed at pH ≥ 5.5 and at a 15-fold excess of EDC relative to COOH. The adduct was evaluated to be a guanidine derivative formed by the reaction of the amine group of CHI directly with EDC. DS ≥ 12 % imparted water solubility to CHI at physiological pH and mPEG-CHI (0.2-1.0 mg/mL) was not cytotoxic against the breast cancer cell lines MCF-7 and MDA-MB-231, indicating its suitability for medical applications.

• Authors: Asim Mushtaq, Li Li, Anitha A, Lisbeth Grøndahl
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 221 Pg. 204-211 (Nov 30 2022) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 36058393 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier B.V.

Chemical References

• monomethoxypolyethylene glycol
• Chitosan
• Polyethylene Glycols
• Carbodiimides

Topics

• Chitosan (chemistry)
• Polyethylene Glycols (chemistry)
• Solubility
• Carbodiimides