Biodegradable double cross-linked chitosan hydrogels for drug delivery: Impact of chemistry on rheological and pharmacological performance

This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the c...

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Veröffentlicht in:International journal of biological macromolecules 2020-12, Vol.165 (Pt B), p.2205-2218
Hauptverfasser: Iglesias, Nieves, Galbis, Elsa, Valencia, Concepción, Díaz-Blanco, M. Jesús, Lacroix, Bertrand, de-Paz, M.-Violante
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container_end_page 2218
container_issue Pt B
container_start_page 2205
container_title International journal of biological macromolecules
container_volume 165
creator Iglesias, Nieves
Galbis, Elsa
Valencia, Concepción
Díaz-Blanco, M. Jesús
Lacroix, Bertrand
de-Paz, M.-Violante
description This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the chosen ionic and covalent cross-linker, respectively. The novel hydrogels completely disintegrated within 96 h by means of a hydrolysis process mediated by the enzyme trehalase. As far as the authors are aware, this is the first time that a trehalose derivative has been used as a covalent cross-linker in the formation of biodegradable hydrogels. The impact of CTS concentration and degree of cov-XrL on rheological parameters were examined by means of an experimental model design and marked differences were found between the materials. Hydrogels with maximum elastic properties were achieved at high CTS concentrations and high degrees of cov-XrL. DCNa-loaded formulations displayed well-controlled drug-release profiles strongly dependent on formulation composition (from 17% to 40% in 72 h). Surprisingly, higher degrees of covalent cross-linking led to a boost in drug release. The formulations presented herein provides a simple and straightforward pathway to design fully biodegradable, tailor-made controlled drug delivery systems with improved rheological properties. [Display omitted] •A biodegradable trehalose-based chemical cross-linker was used for the first time.•Biodegradable double-cross-linked chitosan-based (CTS) hydrogels were prepared.•Impact of CTS conc. and degree of covalent cross-linking on rheological parameters.•A boost in drug release found in formulations with highest levels of cross-linking.•DDS with improved viscoelastic properties exhibited lowest rates of drug release.
doi_str_mv 10.1016/j.ijbiomac.2020.10.006
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subjects Biodegradable
Chemical cross-linking
Chitosan - chemistry
Controlled drug release
Cross-Linking Reagents - chemistry
Delayed-Action Preparations - chemical synthesis
Delayed-Action Preparations - chemistry
Delayed-Action Preparations - pharmacology
Drug Carriers - chemical synthesis
Drug Carriers - chemistry
Drug Carriers - pharmacology
Eco-friendly formulations
Hydrogels - chemistry
Hydrogen-Ion Concentration
Ionic cross-linking
Trehalase - chemistry
Viscoelastic hydrogels
title Biodegradable double cross-linked chitosan hydrogels for drug delivery: Impact of chemistry on rheological and pharmacological performance
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