Dynamic Hydrogels Based on Double Imine Connections and Application for Delivery of Fluorouracil.

Yan Zhang,Eddy Petit,Rui Yu,Chi-Yen Pham,Suming Li,Mihail Barboiu

doi:10.3389/fchem.2020.00739

Abstract

Dynamic hydrogels have been prepared by cross-linking of O-carboxymethyl chitosan (O-CMCS) with reversibly connected imino-PEGylated dynamers. The double imine chitosan/dynamer and dynamer bonds and were used to provide tighter structures and adaptive drug release behaviors of the hydrogels. The structural and physical properties of the resulted hydrogels were examined, showing good thermal stability and higher swelling behaviors (up to 3,000%). When hydrogels with various composition ratios were further applied for delivery of anti-cancer drug fluorouracil (5-FU), high drug encapsulation rates were recorded, up to 97%. The release profile of 5-FU showed fast rate at the beginning, followed by slow increase to the maximum amount within 12 h, demonstrating potential as drug carriers for efficient drug delivery.

Highlights

IntroductionWith the increasing interest of dynamic covalent chemistry from various fields, dynamic polymers—dynamers have presented as a powerful tool to achieve adaptive materials (Aida et al, 2012; Roy et al, 2015; Zhang and Barboiu, 2015, 2016), and found wide applications in biorecognition (Yao et al, 2014; Yasen et al, 2017; Zhang et al, 2020b), materials design (Goor et al, 2017; Zhang et al, 2020c), drug delivery (Bakker et al, 2016), etc
The modulus at gelation point increased from 0.14 to 3.36 Pa, and the gelation time was shortened from 1,850 to 250 s. These results demonstrated that higher content of O-carboxymethyl chitosan (O-CMCS) leads to increased degree of cross-linking between the aldehyde groups of cross-linking PEG dynamer and the amine groups of O-CMCS
Dynamic hydrogels were prepared crosslinking of PEG dynamers with O-carboxymethyl chitosan via amino/carbonyl-imine chemistry

Summary

Introduction

With the increasing interest of dynamic covalent chemistry from various fields, dynamic polymers—dynamers have presented as a powerful tool to achieve adaptive materials (Aida et al, 2012; Roy et al, 2015; Zhang and Barboiu, 2015, 2016), and found wide applications in biorecognition (Yao et al, 2014; Yasen et al, 2017; Zhang et al, 2020b), materials design (Goor et al, 2017; Zhang et al, 2020c), drug delivery (Bakker et al, 2016), etc. According to the cross-linking methods, hydrogels can be formed through non-covalent physical interactions or covalent chemical bonds (Goujon et al, 2017; Gu et al, 2018). In the former case, supramolecular interactions are usually involved for the establishment of hydrogels, including hydrogen bonding, host-guest interactions, etc. (Xiao and Wang, 2018; Xiao et al, 2019; Yu J. et al, 2020) Reversible reactions, such as imine disulfide or esther bond formation, have been applied in hydrogel preparations (Wei et al, 2015; Yamada and Schneider, 2016). PH-responsive polymers based on Schiff-base reaction have been designed and used for delivery and pseudo targeted release of doxorubicin (DOX) (Tao et al, 2018)

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Conclusion