Effect of Protonation State and N-Acetylation of Chitosan on Its Interaction with Xanthan Gum: A Molecular Dynamics Simulation Study.

Suha Dadou,Milan Antonijevic,Samer Alabdallah,Babur Chowdhry,Adnan Badwan,Musa El-Barghouthi

doi:10.3390/md15100298

Suha Dadou, Milan Antonijevic + Show 4 more

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https://doi.org/10.3390/md15100298

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Abstract

Hydrophilic matrices composed of chitosan (CS) and xanthan gum (XG) complexes are of pharmaceutical interest in relation to drug delivery due to their ability to control the release of active ingredients. Molecular dynamics simulations (MDs) have been performed in order to obtain information pertaining to the effect of the state of protonation and degree of N-acetylation (DA) on the molecular conformation of chitosan and its ability to interact with xanthan gum in aqueous solutions. The conformational flexibility of CS was found to be highly dependent on its state of protonation. Upon complexation with XG, a substantial restriction in free rotation around the glycosidic bond was noticed in protonated CS dimers regardless of their DA, whereas deprotonated molecules preserved their free mobility. Calculated values for the free energy of binding between CS and XG revealed the dominant contribution of electrostatic forces on the formation of complexes and that the most stable complexes were formed when CS was at least half-protonated and the DA was ≤50%. The results obtained provide an insight into the main factors governing the interaction between CS and XG, such that they can be manipulated accordingly to produce complexes with the desired controlled-release effect.

Highlights

Over the past three decades, hydrophilic polysaccharides have gained wide scientific interest in relation to drug delivery systems
Free amine groups present in the CS backbone were substituted by acetamide groups (C2 H5 NO) in order to increase the degree of N-acetylation, whereas hydrogen atoms were added to the existing free amine groups (−NH3 + ) to form protonated CS molecules [45]
Complexes of CS–xanthan gum (XG) indicate the preference of CS to interact and penetrate in between the chains of XG when protonation is increased

Summary

Introduction

Over the past three decades, hydrophilic polysaccharides have gained wide scientific interest in relation to drug delivery systems. This is due, in part, to the fact that they are naturally occurring polymers of low toxicity, exhibit high stability, are biocompatible/biodegradable, and show mucoadhesion properties [1,2]. Chitosan (CS) is a hydrophilic, linear polysaccharide composed of repeated β-(1-4) linked units of either 2-amino-2-deoxy-β-D-glucopyranose (glucosamine) or 2-acetamido-2-deoxy-β-D-glucopyranose (glucosacetamide), depending on the degree of N-acetylation (DA) (Figure 1a) [4]. CS is prepared by the deacetylation of chitin, which is mainly found in crustaceans, fungi, and insects [5]. Various numbers of acetamide groups (C2 H5 NO) can be found randomly distributed at the

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