Effects of Chain Length of Chitosan Oligosaccharides on Solution Properties and Complexation with siRNA

Tim Delas (1, 2) , Maxime Mock-Joubert (3) , Jimmy Faivre (3) , Mirjam Hofmaier (1, 2) , Olivier Sandre (1, 2) , François Dole (4) , Jean Paul Chapel (4) , Agnès Crépet (3) , Stéphane Trombotto (3) , Thierry Delair (3) , Christophe Schatz (1, 2)

1 LCPO - Laboratoire de Chimie des Polymères Organiques
2 Team 3 LCPO : Polymer Self-Assembly & Life Sciences
3 IMP - Ingénierie des Matériaux Polymères
4 CRPP - Centre de Recherche Paul Pascal

In the context of gene delivery, chitosan has been widely used as a safe and effective polycation to complex DNA, RNA and more recently, siRNA. However, much less attention has been paid to chitosan oligosaccharides (COS) despite their biological properties. This study proposed to carry out a physicochemical study of COS varying in degree of polymerization (DP) from 5 to 50, both from the point of view of the solution properties and the complexing behavior with siRNA. The main parameters studied as a function of DP were the apparent pKa, the solubility versus pH, the binding affinity with siRNA and the colloidal properties of complexes. Some parameters, like the pKa or the binding enthalpy with siRNA, showed a marked transition from DP 5 to DP 13, suggesting that electrostatic properties of COS vary considerably in this range of DP. The colloidal properties of siRNA/COS complexes were affected in a different way by the COS chain length. In particular, COS of relatively high DP (≥50) were required to form small complex particles with good stability.

Mots clés: polyelectrolyte; oligosaccharide; siRNA; chitosan; electrostatics; polyionic complexation

Domaines: Polymères; Matière Molle [cond-mat.soft]; Biotechnologies

Tim Delas, Maxime Mock-Joubert, Jimmy Faivre, Mirjam Hofmaier, Olivier Sandre, et al.. Effects of Chain Length of Chitosan Oligosaccharides on Solution Properties and Complexation with siRNA. Polymers, 2019, 11 (8), pp.1236. ⟨10.3390/polym11081236⟩. ⟨hal-02194615⟩